Device for agitating the fluid contents of a container

ABSTRACT

An automated analyzer for performing multiple diagnostic assays simultaneously includes multiple stations, or modules, in which discrete aspects of the assay are performed on fluid samples contained in reaction receptacles. The analyzer includes stations for automatically preparing a specimen sample, incubating the sample at prescribed temperatures for prescribed periods, preforming an analyte isolation procedure, and ascertaining the presence of a target analyte. An automated receptacle transporting system moves the reaction receptacles from one station to the next. The analyzer further includes devices for carrying a plurality of specimen tubes and disposable pipette tips in a machine-accessible manner, a device for agitating containers of target capture reagents comprising suspensions of solid support material and for presenting the containers for machine access thereto, and a device for holding containers of reagents in a temperature controlled environment and presenting the containers for machine access thereto. A method for performing an automated diagnostic assay includes an automated process for isolating and amplifying a target analyte. The process is performed by automatically moving each of a plurality of reaction receptacles containing a solid support material and a fluid sample between stations for incubating the contents of the reaction receptacle and for separating the target analyte bound to the solid support from the fluid sample. An amplification reagent is added to the separated analyte after the analyte separation step and before a final incubation step.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of U.S. patent applicationSer. No. 09/985,064 filed Nov. 1, 2001, which is a continuation of U.S.patent application Ser. No. 09/303,030 filed Apr. 30, 1999, now U.S.Pat. No. 6,335,166, which claims the benefit of U.S. ProvisionalApplication No. 60/083,927 filed May 1, 1998.

FIELD OF THE INVENTION

[0002] The present invention relates to an automated analyzer forperforming multiple diagnostic assays simultaneously.

BACKGROUND OF THE INVENTION

[0003] None of the references described or referred to herein areadmitted to be prior art to the claimed invention.

[0004] Diagnostic assays are widely used in clinical diagnosis andhealth science research to detect or quantify the presence or amount ofbiological antigens, cell abnormalities, disease states, anddisease-associated pathogens, including parasites, fungi, bacteria andviruses present in a host organism or sample. Where a diagnostic assaypermits quantification, practitioners may be better able to calculatethe extent of infection or disease and to determine the state of adisease over time. In general, diagnostic assays are based either on thedetection of antigens (immunoassays) or nucleic acids (nucleicacid-based assays) belonging to an organism or virus of interest.

[0005] Nucleic acid-based assays generally include several steps leadingto the detection or quantification of one or more target nucleic acidsequences in a sample which are specific to the organism or virus ofinterest. The targeted nucleic acid sequences can also be specific to anidentifiable group of organisms or viruses, where the group is definedby at least one shared sequence of nucleic acid that is common to allmembers of the group and is specific to that group in the sample beingassayed. The detection of individual and groups of organisms and virusesusing nucleic acid-based methods is fully described by Kohne, U.S. Pat.No. 4,851,330, and Hogan, U.S. Pat. No. 5,541,308.

[0006] The first step in a nucleic acid-based assay is designing a probewhich exhibits specificity, under stringent hybridization conditions,for a nucleic acid sequence belonging to the organism or virus ofinterest. While nucleic acid-based assays can be designed to detecteither deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), ribosomalRNA (rRNA), or the gene encoding rRNA (rDNA), is typically the preferrednucleic acid for detection of a prokaryotic or eukaryotic organism in asample. Ribosomal RNA target sequences are preferred because of theirrelative abundance in cells, and because rRNA contains regions ofsequence variability that can be exploited to design probes capable ofdistinguishing between even closely related organisms. (Ribosomal RNA isthe major structural component of the ribosome, which is the situs ofprotein synthesis in a cell.) Viruses, which do not contain rRNA, andcellular changes are often best detected by targeting DNA, RNA, or amessenger RNA (mRNA) sequence, which is a nucleic acid intermediate usedto synthesize a protein. When the focus of a nucleic acid-based assay isthe detection of a genetic abnormality, then the probes are usuallydesigned to detect identifiable changes in the genetic code, such as theabnormal Philadelphia chromosome associated with chronic myelocyticleukemia. See, e.g., Stephenson et al., U.S. Pat. No. 4,681,840.

[0007] When performing a nucleic acid-based assay, preparation of thesample is necessary to release and stabilize target nucleic acids whichmay be present in the sample. Sample preparation can also serve toeliminate nuclease activity and remove or inactivate potentialinhibitors of nucleic acid amplification (discussed below) or detectionof the target nucleic acids. See, e.g., Ryder et al., U.S. Pat. No.5,639,599, which discloses methods for preparing nucleic acid foramplification, including the use of complexing agents able to complexwith ferric ions contributed by lysed red blood cells. The method ofsample preparation can vary and will depend in part on the nature of thesample being processed (e.g., blood, urine, stool, pus or sputum). Whentarget nucleic acids are being extracted from a white blood cellpopulation present in a diluted or undiluted whole blood sample, adifferential lysis procedure is generally followed. See, e.g., Ryder etal., European Patent Application No. 93304542.9 and European PatentPublication No. 0547267. Differential lysis procedures are well known inthe art and are designed to specifically isolate nucleic acids fromwhite blood cells, while limiting or eliminating the presence oractivity of red blood cell products, such as heme, which can interferewith nucleic acid amplification or detection.

[0008] Before or after exposing the extracted nucleic acid to a probe,the target nucleic acid can be immobilized by target-capture means,either directly or indirectly, using a “capture probe” bound to asubstrate, such as a magnetic bead. Examples of target-capturemethodologies are described by Ranki et al., U.S. Pat. No. 4,486,539,and Stabinsky, U.S. Pat. No. 4,751,177. Target capture probes aregenerally short sequences of nucleic acid (i.e., oligonucleotide)capable of hybridizing, under stringent hybridization conditions, with asequence of nucleic acid which also contains the target sequence.Magnets in close proximity to the reaction vessel are used to draw andhold the magnetic beads to the side of the vessel. Once the targetnucleic acid is thus immobilized, the hybridized nucleic acid can beseparated from non-hybridized nucleic acid by aspirating fluid from thereaction vessel and optionally performing one or more wash steps.

[0009] In most instances, it is desirable to amplify the target sequenceusing any of several nucleic acid amplification procedures which arewell known in the art. Specifically, nucleic acid amplification is theenzymatic synthesis of nucleic acid amplicons (copies) which contain asequence that is complementary to a nucleic acid sequence beingamplified. Examples of nucleic acid amplification procedures practicedin the art include the polymerase chain reaction (PCR), stranddisplacement amplification (SDA), ligase chain reaction (LCR), andtranscription-associated amplification (TAA). Nucleic acid amplificationis especially beneficial when the amount of target sequence present in asample is very low. By amplifying the target sequences and detecting theamplicon synthesized, the sensitivity of an assay can be vastlyimproved, since fewer target sequences are needed at the beginning ofthe assay to better ensure detection of nucleic acid in the samplebelonging to the organism or virus of interest.

[0010] Methods of nucleic acid amplification are thoroughly described inthe literature. PCR amplification, for instance, is described by Mulliset al. in U.S. Pat. Nos. 4,683,195, 4,683,202 and 4,800,159, and inMethods in Enzymology, 155:335-350 (1987). Examples of SDA can be foundin Walker, PCR Methods and Applications, 3:25-30 (1993), Walker et al.in Nucleic Acids Res., 20:1691-1996 (1992) and Proc. Natl. Acad Sci.,89:392-396 (1991). LCR is described in U.S. Pat. Nos. 5,427,930 and5,686,272. And different TAA formats are provided in publications suchas Burg et al. in U.S. Pat. No. 5,437,990; Kacian et al. in U.S. Pat.Nos. 5,399,491 and 5,554,516; and Gingeras et al. in InternationalApplication No. PCT/US87/01966 and International Publication No. WO88/01302, and International Application No. PCT/US88/02108 andInternational Publication No. WO 88/10315.

[0011] Detection of a targeted nucleic acid sequence requires the use ofa probe having a nucleotide base sequence which is substantiallycomplementary to the targeted sequence or, alternatively, its amplicon.Under selective assay conditions, the probe will hybridize to thetargeted sequence or its amplicon in a manner permitting a practitionerto detect the presence of the targeted sequence in a sample. Effectiveprobes are designed to prevent non-specific hybridization with anynucleic acid sequence which will interfere with detecting the presenceof the targeted sequence. Probes may include a label capable ofdetection, where the label is, for example, a radiolabel, fluorescentdye, biotin, enzyme or chemiluminescent compound. Chemiluminescentcompounds include acridinium esters which can be used in a hybridizationprotection assay (HPA) and then detected with a luminometer. Examples ofchemiluminescent compounds and methods of labeling probes withchemiluminescent compounds can be found in Arnold et al., U.S. Pat. Nos.4,950,613, 5,185,439 and 5,585,481; and Campbell et al., U.S. Pat. No.4,946,958.

[0012] HPA is a detection method based on differential hydrolysis whichpermits specific detection of the acridinium ester-labeled probehybridized to the target sequence or amplicon thereof. HPA is describedin detail by Arnold et al. in U.S. Pat. Nos. 5,283,174 and 5,639,604.This detection format permits hybridized probe to be distinguished fromnon-hybridized probe in solution and includes both a hybridization stepand a selection step. In the hybridization step, an excess of acridiniumester-labeled probe is added to the reaction vessel and permitted toanneal to the target sequence or its amplicon. Following thehybridization step, label associated with unhybridized probe is renderednon-chemiluminescent in the selection step by the addition of analkaline reagent. The alkaline reagent specifically hydrolyzes only thatacridinium ester label associated with unhybridized probe, leaving theacridinium ester of the probe: target hybrid intact and detectable.Chemiluminescence from the acridinium ester of the hybridized probe canthen be measured using a luminometer and signal is expressed in relativelight units (RLU).

[0013] After the nucleic acid-based assay is run, and to avoid possiblecontamination of subsequent amplification reactions, the reactionmixture can be treated with a deactivating reagent which destroysnucleic acids and related amplification products in the reaction vessel.Such reagents can include oxidants, reductants and reactive chemicalswhich modify the primary chemical structure of a nucleic acid. Thesereagents operate by rendering nucleic acids inert towards anamplification reaction, whether the nucleic acid is RNA or DNA. Examplesof such chemical agents include solutions of sodium hypochlorite(bleach), solutions of potassium permanganate, formic acid, hydrazine,dimethyl sulfate and similar compounds. More details of a deactivationprotocol can be found in Dattagupta et al., U.S. Pat. No. 5,612,200.

[0014] When performed manually, the complexity and shear number ofprocessing steps associated with a nucleic acid-based assay introduceopportunities for practitioner-error, exposure to pathogens, andcross-contamination between assays. Following a manual format, thepractitioner must safely and conveniently juxtapose the test samples,reagents, waste containers, assay receptacles, pipette tips, aspiratordevice, dispenser device, and magnetic rack for performingtarget-capture, while being especially careful not to confuse racks,test samples, assay receptacles, and associated tips, or to knock overany tubes, tips, containers, or instruments. In addition, thepractitioner must carefully perform aspirating and dispensing steps withhand-held, non-fixed instruments in a manner requiring precise executionto avoid undesirable contact between assay receptacles, aerosolformation, or aspiration of magnetic particles or other substrates usedin a target-capture assay. As a further precaution, the magnetic fieldin a manually performed target-capture assay is often applied to onlyone side of the assay receptacle so that fluids can be aspirated througha pipette tip inserted along the opposite side of the assay receptacle.Although applying a magnetic field to only one side of the assayreceptacle is a less efficient means for performing a target captureassay, it is designed to prevent magnetic particles from beingunnecessarily aspirated as a result of practitioner inaccuracies.

[0015] A need exists for an automated diagnostic analyzer whichaddresses many of the concerns associated with manual approaches toperforming nucleic acid-based assays. In particular, significantadvantages can be realized by automating the various process steps of anucleic acid-based assay, including greatly reducing the risk ofuser-error, pathogen exposure, contamination, and spillage, whilesignificantly increasing through-put volume. Automating the steps of anucleic acid-based assay will also reduce the amount training requiredfor practitioners and virtually eliminate sources of physical injuryattributable to high-volume manual applications.

SUMMARY OF THE INVENTION

[0016] The above-described needs are addressed by an automated clinicalanalyzer constructed and operated in accordance with aspects of thepresent invention. In general, the automated clinical analyzerintegrates and coordinates the operation of various automated stations,or modules, involved in performing one or more assays on a plurality ofreaction mixtures contained in reaction receptacles. The analyzer ispreferably a self-contained, stand alone unit. Assay specimen materialsand reaction receptacles, as well as the various solutions, reagents,and other materials used in performing the assays are preferably storedwithin the analyzer, as are the waste products generated when assays areperformed.

[0017] The analyzer includes a computer controller which runsanalyzer-controlling and assay-scheduling software to coordinateoperation of the stations of the analyzer and movement of each reactionreceptacle through the analyzer.

[0018] Reaction receptacles can be loaded in an input queue whichsequentially presents each receptacle at a pick-up position to beretrieved by a transport mechanism, which automatically transports thereaction receptacles between the stations of the analyzer.

[0019] Specimen containers are carried on a first ring assembly, anddisposable pipette tips are carried on a second ring assembly.Containers of target capture reagent, including a suspension of solidsupport material, are carried on an inner rotatable assembly constructedand arranged to selectively agitate the containers or present thecontainers for access by the probe of an automatic robotic pipettesystem. Reaction mixtures, including fluid specimen material and targetcapture reagent, are prepared by the pipette system within each reactionreceptacle.

[0020] The analyzer further includes receptacle mixers for mixing thecontents of a receptacle placed therein. The mixer may be in fluidcommunication with fluid containers and may include dispensers fordispensing one or more fluids into the receptacle. One or moreincubators carry multiple receptacles in a temperature-controlledchamber and permit individual receptacles to be automatically placedinto and removed from the chamber. Magnetic separation wash stationsautomatically perform a magnetic separation wash procedure on thecontents of a receptacle placed in the station.

[0021] In the preferred method of operation, assay results may beascertained by the amount of light emitted from a receptacle at theconclusion of the appropriate preparation steps. Accordingly, theanalyzer includes a luminometer for detecting and/or quantifying theamount of light emitted by the contents of the reaction receptacle. Adeactivation queue may be provided to deactivate the contents of areaction receptacle placed therein at the conclusion of the assay.

[0022] Reaction receptacles can be independently transported betweenstations by the transport mechanism, and the stations can be operated inparallel to perform different assay procedures simultaneously ondifferent reaction receptacles, thereby facilitating efficient, highthrough-put operation of the analyzer. Moreover, the present inventionfacilitates arranging the various stations associated with a nucleicacid-based assay onto a single, contained platform, thereby achievingefficient space utilization.

[0023] Other objects, features, and characteristics of the presentinvention, including the methods of operation and the function andinterrelation of the elements of structure, will become more apparentupon consideration of the following description and the appended claims,with reference to the accompanying drawings, all of which form a part ofthis disclosure, wherein like reference numerals designate correspondingparts in the various figures.

DESCRIPTION OF THE DRAWINGS

[0024]FIG. 1 is a perspective view of an automated nucleic acid-baseddiagnostic analyzer according to the present invention;

[0025]FIG. 2 is a perspective view of the structural frame of theanalyzer of the present invention;

[0026]FIG. 3 is a plan view of a portion of the assay processing deck ofthe analyzer of the present invention;

[0027]FIG. 4 is an exploded perspective view of the assay processingdeck;

[0028]FIG. 5 is a plan view of a specimen ring and a pipette tip wheelof the assay processing deck of the analyzer of the present invention;

[0029]FIG. 6 is a perspective view showing the specimen ring and thepipette tip wheel;

[0030]FIG. 6A is a partial cross-sectional view along the line 6A-6A inFIG. 5,

[0031]FIG. 7 is a perspective view of a multi-axis mixer of theprocessing deck of the analyzer of the present invention;

[0032]FIG. 8 is a plan view of the multi-axis mixer;

[0033]FIG. 9 is a side elevation of the multi-axis mixer;

[0034]FIG. 10 is a plan view of the multi-axis mixer with containerholders and a turntable cover removed therefrom;

[0035]FIG. 11 is a cross-sectional view of the multi-axis mixer taken inthe direction 11-11 in FIG. 10;

[0036]FIG. 12 is a perspective view of a drive assembly of themulti-axis mixer;

[0037]FIG. 13 is a perspective view of a transport mechanism of theprocessing deck of the analyzer of the present invention;

[0038]FIG. 14 is a perspective view of a manipulating hook mountingplate and a manipulating hook actuating mechanism of the transportmechanism, with the manipulating hook member engaged with a reactionreceptacle and in a retracted position;

[0039]FIG. 15 is the same as FIG. 14, except with the manipulating hookmember in the extended position;

[0040]FIG. 16 is an exploded perspective view of the transportmechanism;

[0041]FIG. 17 is a side-elevation of a temperature ramping station ofthe processing deck of the analyzer of the present invention;

[0042]FIG. 18 is a front-elevation of the temperature ramping station;

[0043]FIG. 19 is a perspective view of a rotary incubator of theprocessing deck of the analyzer of the present invention;

[0044]FIG. 20 is an exploded view of a portion of a housing and accessopening closure mechanisms according to a first embodiment of the rotaryincubator;

[0045]FIG. 21 is a partial view of a skewed disk linear mixer of therotary incubator, shown engaged with a reaction receptacle employed in apreferred mode of operation of the analyzer of the present invention;

[0046]FIG. 22 is an exploded perspective view of the first embodiment ofthe rotary incubator;

[0047]FIG. 23 is a perspective view of the rotary incubator according toa second embodiment thereof;

[0048]FIG. 23A is an exploded perspective view of the second embodimentof the rotary incubator;

[0049]FIG. 23B is a partial exploded perspective view of an accessopening closure mechanism of the second embodiment of the rotaryincubator;

[0050]FIG. 23C is an exploded view of a receptacle carrier carousel ofthe second embodiment of the rotary incubator;

[0051]FIG. 24 is a perspective view of a magnetic separation washstation of the processing deck of the present invention with a sideplate thereof removed;

[0052]FIG. 25 is a partial transverse cross-section of the magneticseparation wash station,

[0053]FIG. 25A is a partial transverse cross-section of a tip of anaspirating tube of the magnetic separation wash station with acontamination-limiting tiplet carried on the end thereof;

[0054]FIG. 26 is an exploded perspective view of a receptacle carrierunit, an orbital mixer assembly, and a divider plate of the magneticseparation wash station;

[0055]FIG. 27 is a partial cross-sectional view of a wash bufferdispenser nozzle, an aspirator tube with a contamination-limiting tipletengaged with an end thereof, and a receptacle carrier unit of themagnetic separation wash station, showing a multi-tube unit reactionreceptacle employed in a preferred mode of operation of the analyzercarried in the receptacle carrier unit and the aspirator tube andcontamination-limiting tiplet inserted into a receptacle vessel of themulti-tube unit;

[0056]FIG. 28 is a partial cross-sectional view of the wash bufferdispenser nozzle, the aspirator tube, and the receptacle carrier unit ofthe magnetic separation wash station, showing the multi-tube unitcarried in the receptacle carrier unit and the aspirator tube engagingthe contamination-limiting tiplet held in a contamination-limitingelement holding structure of the multi-tube unit;

[0057] FIGS. 29A-29D show a partial cross-section of a first embodimentof a tiplet stripping hole of a tiplet stripping plate of the magneticseparation wash station and a tiplet stripping operation using thetiplet stripping hole;

[0058] FIGS. 30A-30D show a partial cross-section of a second embodimentof a tiplet stripping hole and a tiplet stripping operation using thetiplet stripping hole;

[0059]FIG. 31A is a plan view of a third embodiment of a tipletstripping hole of a tiplet stripping plate of the magnetic separationwash station;

[0060] FIGS. 31B-31C show a partial cross-section of the thirdembodiment of the tiplet stripping hole and a tiplet stripping operationusing the tiplet;

[0061]FIG. 32 is a perspective view of an orbital mixer with a frontplate thereof removed;

[0062]FIG. 33 is an exploded view of the orbital mixer of the processingdeck of the analyzer of the present invention;

[0063]FIG. 34 is a top-plan view of the orbital mixer;

[0064]FIG. 35 is a top perspective view of a reagent cooling bay of theprocessing deck of the analyzer of the present invention;

[0065]FIG. 36 is a top perspective view of a reagent cooling bay withthe container tray removed therefrom;

[0066]FIG. 37 is a bottom plan view of the reagent cooling bay;

[0067]FIG. 38 is an exploded view of the reagent cooling bay;

[0068]FIG. 39 is a top perspective view of a modular container tray ofthe reagent cooling bay;

[0069]FIG. 40 is a perspective view of a first embodiment of aluminometer of the processing deck of the analyzer of the presentinvention;

[0070]FIG. 41 is a partial exploded perspective view of the luminometerof the first embodiment;

[0071]FIG. 42A is a partial perspective view of a receptacle transportmechanism of the first embodiment of the luminometer;

[0072]FIG. 42B is an end view of the receptacle transport mechanism ofthe first embodiment of the luminometer;

[0073]FIG. 42C is a top view of the receptacle transport mechanism ofthe first embodiment of the luminometer;

[0074]FIG. 43 is a break away perspective view of a second embodiment ofthe luminometer of the present invention;

[0075]FIG. 44 is an exploded perspective view of a multi-tube unit doorassembly for the luminometer of the second embodiment;

[0076]FIG. 45 is an exploded perspective view of a shutter assembly fora photosensor aperture for the luminometer of the second embodiment;

[0077]FIG. 45A is a perspective view of an aperture plate of the shutterassembly of the luminometer of the second embodiment;

[0078]FIG. 46 is a perspective view of a receptacle vessel positionerassembly of the luminometer of the second embodiment, including areceptacle vessel positioner disposed within a receptacle vesselpositioner frame;

[0079]FIG. 47 is a perspective view of the receptacle vessel positioner;

[0080]FIG. 48 is a side elevation of the receptacle vessel positionerassembly;

[0081]FIG. 49 is a perspective view showing the receptacle vesselpositioner of the receptacle vessel positioner assembly operativelyengaging a multi-tube unit employed in a preferred mode of operation ofthe analyzer;

[0082]FIG. 50 is a perspective view of a multi-tube unit transportmechanism of the luminometer of the second embodiment;

[0083]FIG. 51 is a partial perspective view showing a multi-tube unittransport and drive screw of the multi-tube unit transport mechanism ofthe luminometer;

[0084]FIG. 52 is a perspective view of a lower chassis of the analyzerof the present invention;

[0085]FIG. 53 is a perspective view of a right-side drawer of the lowerchassis;

[0086]FIG. 54 is a perspective view of a left-side drawer of the lowerchassis;

[0087]FIG. 55 is a perspective view of a specimen tube tray employed ina preferred mode of operation of the analyzer of the present invention;

[0088]FIG. 56 is a top plan view of the specimen tube tray;

[0089]FIG. 57 is a partial cross-section of the specimen tube traythrough line “57-57z” FIG. 55;

[0090]FIG. 58 is a perspective view of a multi-tube unit employed in apreferred mode of operation of the analyzer of the present invention;

[0091]FIG. 59 is a side elevation of a contact-limiting pipette tipletemployed in a preferred mode of operation of the analyzer of the presentinvention and carried on the multi-tube unit shown in FIG. 58; and

[0092]FIG. 60 is an enlarged bottom view of a portion of the multi-tubeunit, in the direction of arrow “60” in FIG. 58.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0093] Analyzer Overview

[0094] An automated diagnostic analyzer according to the presentinvention is designated generally by reference number 50 in FIGS. 1 and2. Analyzer 50 includes a housing 60 built over an internal framestructure 62, preferably made of steel. The analyzer 50 is preferablysupported on caster wheels 64 structurally mounted to the framestructure 62 so as to make the analyzer movable.

[0095] The various stations involved in performing an automated assayand the assay specimens are housed within housing 60. In addition, thevarious solutions, reagents, and other materials used in performing theassays are preferably stored within the housing 60, as are the wasteproducts generated when assays are performed with the analyzer 50.

[0096] Housing 60 includes a test receptacle loading opening 68, whichis shown in FIG. 1 to be disposed in a forwardly facing panel of thehousing 60, but could as well be located in other panels of the housing60. A pipette door 70 having a view window 72 and a carousel door 74having a view window 76 are disposed above a generally horizontal worksurface 66. A forwardly protruding arcuate panel 78 accommodates aspecimen carousel, which will be described below. A flip-up arcuatespecimen door 80 is pivotally attached to the housing so as to bevertically pivotal with respect to arcuate panel 78 so as to provideaccess to a forward portion of the specimen carousel behind the panel78. Sensors indicate when the doors are closed, and the specimen door80, the carousel door 74, and the pipette door 70 are locked duringanalyzer operation. The locking mechanism for each door preferablyconsists of a hook attached to a DC rotary solenoid (rated forcontinuous duty) with a spring return. Preferred rotary solenoids areavailable from Lucas Control Systems, of Vandalia, Ohio, model numbersL-2670-034 and L-1094-034.

[0097] An extension portion 102, preferably made of a transparent ortranslucent material, extends above the top portion of housing 60 so asto provide vertical clearance for moving components within the housing60.

[0098] The assays are performed primarily on a processing deck 200,which is the general location of the various assay stations of theanalyzer 50 described below. For simplicity of the illustration, theprocessing deck 200 is shown in FIG. 2 without any of the assay stationsmounted thereon. The processing deck 200 comprises a datum plate 82 towhich the various stations are directly or indirectly mounted. Datumplate 82 preferably comprises a machined aluminum plate. The processingdeck 200, also known as the chemistry deck, separates the interior ofthe housing into the chemistry area, or upper chassis, above the datumplate 82 and the storage areas, or lower chassis 1100, located below thedatum plate 82.

[0099] A number of fans and louvers are preferably provided in the upperchassis portion of the housing 60 to create air circulation throughoutthe upper chassis to avoid excessive temperatures in the upper chassis.

[0100] As the analyzer 50 of the present invention is computercontrolled, the analyzer 50 includes a computer controller,schematically represented as box 1000 in FIG. 2, which runs high-levelanalyzer-controlling software known as the “assay manager program”. Theassay manager program includes a scheduler routine which monitors andcontrols test specimen movement through the chemistry deck 200.

[0101] The computer controller 1000 which controls the analyzer 50 mayinclude a stand-alone computer system including a CPU, keyboard,monitor, and may optionally include a printer device. A portable cartmay also be provided for storing and supporting the various computercomponents. Alternately, the computer hardware for running theanalyzer-controlling software may be integrally housed within thehousing 60 of the analyzer 50.

[0102] Low level analyzer control, such as control of electric motorsand heaters used throughout the analyzer 50 and monitoring of fluidlevels within bulk fluid and waste fluid containers, is performed by anembedded controller, preferably comprising a Motorola 68332microprocessor. Stepper motors used throughout the analyzer are alsopreferably controlled by preprogrammed, off-the-shelf, microprocessorchips available from E-M Technologies, Bala Cynwyd, Pa.

[0103] The processing deck 200 is shown schematically in FIGS. 3 and 4.FIG. 3 represents a schematic plan view of a portion of the processingdeck 200, and FIG. 4 represents a schematic perspective view of theprocessing deck. The datum plate 82 forms the foundation of theprocessing deck 200 on which all stations are directly or indirectlyattached.

[0104] Processing deck 200 includes a reaction receptacle input queue150 which extends from opening 68 in front of housing 60. A plurality ofreaction receptacles are loaded in a stacked fashion in the input queue150. The purpose of the input queue is to hold a prescribed number ofreaction receptacles and to sequentially present them at a pick-upposition to be retrieved by a transport mechanism (described below). Areflective sensor at the pick-up position verifies the presence of areceptacle at that position. The input queue also includes a device forcounting the number of receptacles resident therein at any given time.

[0105] A reaction receptacle shuttle assembly (not shown) within thequeue moves the receptacles along a receptacle advance path toward thepick-up position. Optical sensors indicate when the shuttle assembly isin its home and fully extended positions. The queue includes a drawerwhich may be pulled out for loading the receptacles therein. Before thedrawer is opened, however, it must be unlocked and the shuttle mustdisengage from the receptacle advance path. When the drawer is againclosed, it is locked and the shuttle engages the receptacles and movesthem toward the pick-up position. Optical sensors indicate when thedrawer is closed and when the shuttle has engaged a receptacle. As eachreceptacle is removed from the pick-up position by the transportmechanism, the receptacle shuttle advances the receptacles onereceptacle-width, so that the next receptacle is in the pick-upposition.

[0106] The reaction receptacles are preferably integrally formed lineararrays of test tubes and known as multi-tube units, or MTUs. Thepreferred reaction receptacles (MTUs) will be described in more detailbelow.

[0107] A first ring assembly, which in the preferred embodimentcomprises a specimen ring 250, is mounted on a pivoting jig plate 130 ata distance above the datum plate 82. Specimen ring 250 is generallycircular and preferably holds up to nine specimen trays 300 in anannular fluid container carrier portion thereof, and each of thespecimen trays preferably holds 20 specimen-containing containers, ortest tubes 320. The specimen ring 250 is constructed and arranged to berotatable about a first generally vertical axis of rotation and deliversthe specimen tubes 320 to a specimen pipette assembly 450, preferably anautomated robotic pipette system. The forward portion of specimen ring250 is accessible through the flip-up carousel door 80 provided inhousing 60 so that trays 300 of test tubes 320 can be easily loaded ontothe specimen ring 250 and unloaded from the specimen ring. Specimen ring250 is driven by a motor, as will be described in more detail below.

[0108] A second ring assembly, which in the preferred embodimentcomprises a pipette tip wheel 350, is located in an interior portion ofthe specimen ring 250, so that at least a portion of the outer perimeterof the pipette tip wheel 350 is disposed radially inwardly of the innerperiphery of the ring 250. Pipette tip wheel 350 carries thereon aplurality of commercially available packages of pipette tips. Pipettetip wheel 350 is motor driven to rotate independently of specimen ring250 about a second axis of rotation that is generally parallel to thefirst axis of rotation of the specimen ring 250.

[0109] An inner rotatable assembly constructed and arranged to carry aplurality of fluid containers is provided at an interior portion of thepipette tip wheel 350. In the preferred embodiment, the inner rotatableassembly comprises a multi-axis mixer 400 located radially inside thepipette tip wheel 350 (i.e., the second ring assembly) and specimen ring250 (i.e., the first ring assembly). The multi-axis mixer 400 includes arotating turntable 414 that is rotatable about a third axis of rotationthat is generally parallel to the first and second axes of rotation andon which are mounted four independently and eccentrically rotatingcontainer holders 406. Each of the container holders 406 receives acontainer, preferably in the form of a plastic bottle, containing afluid suspension of magnetic particles with immobilized polynucleotidesand polynucleotide capture probes. Each container holder 406 isgenerally cylindrical in shape and includes an axis of symmetry, or axisof rotation. The multi-axis mixer 400 rotates each of the containerseccentrically with respect to the center of the holder 406, whilesimultaneously rotating the turntable 414 about its center so as toprovide substantially constant agitation of the containers to maintainthe magnetic particles in suspension within the fluid.

[0110] The specimen pipette assembly, or robot, 450 is mounted to theframe structure 62 (see FIG. 2) in a position above the specimen ring250 and pipette tip wheel 350. The specimen pipette assembly 450includes a pipette unit 456 having a tubular probe 457 mounted on agantry assembly to provide X, Y, Z motion. Specifically, the pipetteunit 456 is linearly movable in the Y-direction along a track 458 formedin a lateral rail 454, and the lateral rail 454 is longitudinallymovable in the X-direction along a longitudinal track 452. The pipetteunit 456 provides vertical, or Z-axis motion of the probe 457. Drivemechanisms within the specimen pipette assembly 450 position the pipetteunit 456 to the correct X, Y, Z coordinates within the analyzer 50 topipette fluids, to wash the probe 457 of the pipette unit 456, todiscard a protective tip from an end of the probe 457 of the pipetteunit 456, or to stow the pipette unit 456 during periods of nonuse,e.g., in a “home” position. Each axis of the specimen pipette assembly450 is driven by a stepper motor in a known and conventional manner.

[0111] The pipette assembly is preferably an off-the-shelf product.Presently preferred is the Robotic Sample Processor, model numberRSP9000, available from Cavro Inc. of Sunnyvale, Calif. This modelincludes a single gantry arm.

[0112] The specimen pipette assembly 450 is preferably coupled to asyringe pump (not shown) (the Cavro XP 3000 has been used) and a DCdriven diaphragm system fluid wash pump (not shown). The syringe pump ofthe specimen pipette assembly 450 is preferably mounted to the internalframe structure 62 within the housing 60 of the analyzer 50 at aposition above the left-hand side of the chemistry deck 200 and isconnected to pipette unit 456 by suitable tubing (not shown) or otherconduit structures.

[0113] A specimen preparation opening 252 is provided in the jig plate130, so that the specimen pipette assembly 450 can access a reactionreceptacle 160 in the input queue 150 located below the jig plate 130.

[0114] The specimen pipette assembly 450 of the analyzer 50 engagesspecimen tubes 320 carried on the specimen ring 250 through openings140, 142 of an elevated cover plate 138 and engages pipette tips carriedon the pipette tip wheel 350 near the back portions of the specimen ring250 and pipette tip wheel 350, respectively. Accordingly, an operatorcan have access to the forward portions of specimen ring 250 and pipettetip wheel 350 through the carousel door opening 80 during operation ofthe analyzer without interfering with pipetting procedures.

[0115] A tip wash/disposal station 340 is disposed adjacent to thespecimen ring 250 on the jig plate 130. Station 340 includes a tipdisposal tube 342 and a wash station basin 346. During specimenpreparation, the pipette unit 456 of the specimen pipette assembly 450can move into position above the wash station basin 346 where thetubular probe 457 can be washed by pumping distilled water through theprobe 457, the basin of the wash station 346 being connected, preferablyby a flexible hose (not shown), to a liquid waste container in the lowerchassis 1100.

[0116] The tip disposal tube 342 comprises an upstanding tubular member.During specimen transfer from a specimen tube 320 to a reactionreceptacle 160, an elongated pipette tip is frictionally secured ontothe end of the tubular probe 457 of the pipette unit 456, so thatspecimen material does not come into contact with the tubular probe 457of the pipette unit 456 when material is drawn from a specimen tube 320and into the elongated pipette tip. After a specimen has beentransferred from a specimen tube 320, it is critical that the pipettetip used in transferring that specimen not be used again for anotherunrelated specimen. Therefore, after specimen transfer, the pipette unit456 moves to a position above the tip disposal tube 342 and ejects theused, disposable pipette tip into the tip disposal tube 342 which isconnected to one of the solid waste containers carried in the lowerchassis 1100.

[0117] An elongated pipette tip is preferably also frictionally securedto the probe 457 for transferring target capture reagent from containerscarried on the multi-axis mixer 400 to a reaction receptacle 160.Following reagent transfer, the pipette tip is discarded.

[0118] As noted, the specimen ring 250, the pipette tip wheel 350, andthe multi-axis mixer 400 are preferably mounted on a hinged jig plate130 (see FIGS. 5 and 6) supported above the datum plate 82. The jigplate 130 is hinged at a back end 132 thereof (see FIG. 6) so that theplate, and the ring 250, the wheel 350, and the mixer 400 mountedthereon, can be pivoted upwardly to permit access to the area of thechemistry deck below the jig plate.

[0119] A first, or right-side, transport mechanism 500 is mounted on thedatum plate 82 below the jig plate 130 and specimen ring 250 ongenerally the same plane as the input queue 150. Transport mechanism 500includes a rotating main body portion 504 defining a receptacle carrierassembly and an extendible manipulating hook 506 mounted within the mainbody 504 and extendible and retractable with respect thereto by means ofa powered hook member drive assembly. Each of the reaction receptacles160 preferably includes manipulating structure that can be engaged bythe extendible manipulating hook 506, so that the transport mechanism500 can engage and manipulate a reaction receptacle 160 and move it fromone location on the processing deck 200 to another as the reactionreceptacle is sequentially moved from one station to another during theperformance of an assay within the reaction receptacle 160.

[0120] A second, or left-side, transport mechanism 502, of substantiallyidentical construction as first transport mechanism 500, is alsoincluded on the processing deck 200.

[0121] A plurality of receptacle parking stations 210 are also locatedbelow the jig plate 130. The parking stations 210, as their nameimplies, are structures for holding specimen-containing reactionreceptacles until the assay performing stations of the processing deck200 of the analyzer 50 are ready to accept the reaction receptacles. Thereaction receptacles are retrieved from and inserted into the parkingstations 210 as necessary by the transport mechanism 500.

[0122] A right-side orbital mixer 550 is attached to the datum plate 82and receives reaction receptacles 160 inserted therein by the right-sidetransport mechanism 500. The orbital mixer is provided to mix thecontents of the reaction receptacle 160. After mixing is complete, theright-side transport mechanism 500 removes the reaction receptacle fromthe right-side orbital mixer 550 and moves it to another location in theprocessing deck.

[0123] A number of incubators 600, 602, 604, 606, of substantiallyidentical construction are provided. Incubators 600, 602, 604, and 606are preferably rotary incubators. Although the particular assay to beperformed and the desired throughput will determine the desired numberof necessary incubators, four incubators are preferably provided in theanalyzer 50.

[0124] As will be described in more detail below, each incubator (600,602, 604, 606) has a first, and may also have a second, receptacleaccess opening through which a transport mechanism 500 or 502 can inserta reaction receptacle 160 into the incubator or retrieve a reactionreceptacle 160 from the incubator. Within each incubator (600, 602, 604,606) is a rotating receptacle carrier carousel which holds a pluralityof reaction receptacles 160 within individual receptacle stations whilethe receptacles are being incubated. For the nucleic acid-baseddiagnostic assay preferably performed on the analyzer 50 of the presentinvention, first rotary incubator 600 is a target capture and annealingincubator, second rotary incubator 602 is an active temperature andpre-read cool-down incubator (also known as an “AT incubator”), thirdrotary incubator 604 is an amplification incubator, and fourth rotaryincubator 606 is a hybridization protection assay incubator. Theconstruction, function, and role of the incubators in the overallperformance of the assay will be described in more detail below.

[0125] The processing deck 200 preferably also includes a plurality oftemperature ramping stations 700. Two such stations 700 are shownattached to the datum plate 82 between incubators 602 and 604 in FIG. 3.Additional ramping stations may be disposed at other locations on theprocessing deck 200 where they will be accessible by one of thetransport mechanisms 500, 502.

[0126] A reaction receptacle 160 may be placed into or removed from atemperature ramping station 700 by either transport mechanism 500 or502. Each ramping station 700 either raises or lowers the temperature ofthe reaction receptacle and its contents to a desired temperature beforethe receptacle is placed into an incubator or another temperaturesensitive station. By bringing the reaction receptacle and its contentsto a desired temperature before inserting it into one of the incubators(600, 602, 604, 606), temperature fluctuations within the incubator areminimized.

[0127] The processing deck 200 also includes magnetic separation washstations 800 for performing a magnetic separation wash procedure. Eachmagnetic separation wash station 800 can accommodate and perform a washprocedure on one reaction receptacle 160 at a time. Therefore, toachieve the desired throughput, five magnetic separation wash stations800 working in parallel are preferred. Receptacles 160 are inserted intoand removed from the magnetic separation wash stations 800 by theleft-side transport mechanism 502.

[0128] A reagent cooling bay 900 is attached to the datum plate 82roughly between the incubators 604 and 606. Reagent cooling bay 900comprises a carousel structure having a plurality of containerreceptacles for holding bottles of temperature sensitive reagents. Thecarousel resides within a cooled housing structure having a lid withpipette-access holes formed therein.

[0129] A second, or left-side, orbital mixer 552, substantiallyidentical to right-side orbital mixer 550, is disposed betweenincubators 606 and 604. The left-side orbital mixer 552 includesdispenser nozzles and lines for dispensing fluids into the reactionreceptacle resident within the left-side orbital mixer 552.

[0130] A reagent pipette assembly, or robot, 470 includes a doublegantry structure attached to the frame structure 62 (see FIG. 2) and isdisposed generally above the incubators 604 and 606 on the left-handside of the processing deck 200. Specifically, reagent pipette assembly470 includes pipette units 480 and 482. Pipette unit 480 includes atubular probe 481 and is mounted for linear movement, generally in theX-direction, along track 474 of lateral rail 476, and pipette unit 482,including a tubular probe 483, is also mounted for linear motion,generally in the X-direction, along track 484 of lateral rail 478.Lateral rails 476 and 478 can translate, generally in a Y-direction,along the longitudinal track 472. Each pipette unit 480, 482 providesindependent vertical, or Z-axis, motion of the respective probe 481,483. Drive mechanisms within the assembly 470 position the pipette units480, 482 to the correct X, Y, Z coordinates within the analyzer 50 topipette fluids, to wash the tubular probes 481, 483 of the respectivepipette units 480, 482, or to stow the pipette units 480, 482 duringperiods of nonuse, e.g., in “home” positions. Each axis of the pipetteassembly 470 is driven by a stepper motor.

[0131] The reagent pipette assembly 470 is preferably an off-the-shelfproduct. The presently preferred unit is the Cavro Robotic SampleProcessor, model RSP9000, with two gantry arms.

[0132] The pipette units 480, 482 of the reagent pipette assembly 470are each preferably coupled to a respective syringe pump (not shown)(the Cavro XP 3000 has been used) and a DC driven diaphragm system fluidwash pump. The syringe pumps of the reagent pipette assembly 470 arepreferably mounted to the internal frame structure 62 within the housing60 of the analyzer 50 at a position above the left-hand side of thechemistry deck 200 and are connected to the respective pipette units480, 482 by suitable tubing (not shown) or other conduit structures.

[0133] Each pipette unit 480, 482 preferably includes capacitive levelsensing capability. Capacitive level sensing, which is generally knownin the medical instrumentation arts, employs capacitance changes whenthe dielectric of a capacitor, formed by the pipette unit as one plateof the capacitor and the structure and hardware surrounding a containerengaged by the pipette unit as the opposite plate, changes from air tofluid to sense when the probe of the pipette unit has penetrated fluidwithin a container. By ascertaining the vertical position of the probeof the pipette unit, which may be known by monitoring the stepper motorwhich drives vertical movement of the pipette unit, the level of thefluid within the container engaged by the pipette unit may bedetermined.

[0134] Pipette unit 480 transfers reagents from the reagent cooling bay900 into reaction receptacles disposed within the incubator 606 or theorbital mixer 552, and pipette unit 482 transfers reagent materials fromthe reagent cooling bay 900 into reaction receptacles disposed withinthe amplification incubator 604 or the orbital mixer 552.

[0135] The pipette units 480, 482 use capacitive level sensing toascertain fluid level within a container and submerge only a smallportion of the end of the probe of the pipette unit to pipette fluidfrom the container. Pipette units 480, 482 preferably descend as fluidis pipetted into the respective tubular probes 481, 483 to keep the endof the probes submerged to a constant depth. After drawing reagent intothe tubular probe of the pipette unit 480 or 482, the pipette unitscreate a minimum travel air gap of 10 μl in the end of the respectiveprobe 481 or 483 to ensure no drips from the end of the probe as thepipette unit is moved to another location above the chemistry deck 200.

[0136] The results of the assay preferably performed in the analyzer 50of the present invention are ascertained by the amount ofchemiluminescence, or light, emitted from a receptacle vessel 162 at theconclusion of the appropriate preparation steps. Specifically, theresults of the assay are determined from the amount of light emitted bylabel associated with hybridized polynucleotide probe at the conclusionof the assay. Accordingly, the processing deck 200 includes aluminometer 950 for detecting and/or quantifying the amount of lightemitted by the contents of the reaction receptacle. Briefly, theluminometer 950 comprises a housing through which a reaction receptacletravels under the influence of a transport mechanism, a photomultipliertube, and associated electronics. Various luminometer embodiments willbe described in detail below.

[0137] The processing deck 200 also preferably includes a deactivationqueue 750. The assay performed in the analyzer 50 involves the isolationand amplification of nucleic acids belonging to at least one organism orcell of interest. Therefore, it is desirable to deactivate the contentsof the reaction receptacle 160, typically by dispensing a bleach-basedreagent into the reaction receptacle 160 at the conclusion of the assay.This deactivation occurs within the deactivation queue 750.

[0138] Following deactivation, the deactivated contents of the reactionreceptacle 160 are stored in one of the liquid waste containers of thelower chassis 1100 and the used reaction receptacle is discarded into adedicated solid waste container within the lower chassis 1100. Thereaction receptacle is preferably not reused.

[0139] Analyzer Operation

[0140] The operation of the analyzer 50, and the construction,cooperation, and interaction of the stations, components, and modulesdescribed above will be explained by describing the operation of theanalyzer 50 on a single test specimen in the performance of one type ofassay which may be performed with analyzer 50. Other diagnostic assays,which require the use of one or more of the stations, components, andmodules described herein, may also be performed with the analyzer 50.The description herein of a particular assay procedure is merely for thepurpose of illustrating the operation and interaction of the variousstations, components, and modules of the analyzer 50 and is not intendedto be limiting. Those skilled in the art of diagnostic testing willappreciate that a variety of chemical and biological assays can beperformed in an automated fashion with the analyzer 50 of the presentinvention.

[0141] The analyzer 50 is initially configured for an assay run byloading bulk fluids into the bulk fluid storage bay of the lower chassis1100 and connecting the bulk fluid containers to the appropriate hoses(not shown).

[0142] The analyzer is preferably powered up in a sequential process,initially powering the stations, or modules, that will be needed earlyin the process, and subsequently powering the stations that will not beneeded until later in the process. This serves to conserve energy andalso avoids large power surges that would accompany full analyzerpower-up and which could trip circuit breakers. The analyzer alsoemploys a “sleep” mode during periods of nonuse. During sleep mode, aminimal amount of power is supplied to the analyzer, again to avoidlarge surges necessary to power-up an analyzer from complete shut-down.

[0143] A number of reaction receptacles 160, preferably in the form ofplastic, integrally formed multiple-tube units (MTUs), which aredescribed in more detail below, are located through opening 68 into theinput queue 150. Henceforth, the reaction receptacles 160 will bereferred to as MTUs, consistent with the preferred manner of analyzer50.

[0144] The reaction receptacle shuttle assembly (not shown) within theinput queue 150 moves the MTUs 160 from the loading opening 68 to thepick-up position at the end of the queue 150. The right-side transportmechanism 500 takes an MTU 160 from the end of the queue 150 and movesto a bar code reader (not shown) to read the unique bar code label onthat MTU which identifies that MTU. From the bar code reader, the MTU ismoved to an available specimen transfer station 255 below opening 252.

[0145] Multiple Tube Units

[0146] As shown in FIG. 58, an MTU 160 comprises a plurality ofindividual receptacle vessels 162, preferably five. The receptaclevessels 162, preferably in the form of cylindrical tubes with open topends and closed bottom ends, are connected to one another by aconnecting rib structure 164 which defines a downwardly facing shoulderextending longitudinally along either side of the MTU 160.

[0147] The MTU 160 is preferably formed from injection moldedpolypropylene. The most preferred polypropylene is sold by MontellPolyolefins, of Wilmington, Del., product number PD701NW. The Montellmaterial is used because it is readily moldable, chemically compatiblewith the preferred mode of operation of the analyzer 50, and has alimited number of static discharge events which can interfere withaccurate detector or quantification or quantification ofchemiluminescence.

[0148] An arcuate shield structure 169 is provided at one end of the MTU160. An MTU manipulating structure 166 to be engaged by one of thetransport mechanisms 500, 502 extends from the shield structure 169. MTUmanipulating structure 166 comprises a laterally extending plate 168extending from shield structure 169 with a vertically extending piece167 on the opposite end of the plate 168. A gusset wall 165 extendsdownwardly from lateral plate 168 between shield structure 169 andvertical piece 167.

[0149] As shown in FIG. 60 the shield structure 169 and vertical piece167 have mutually facing convex surfaces. The MTU 160 is engaged by thetransport mechanisms 500, 502 and other components, as will be describedbelow, by moving an engaging member laterally (in the direction “A”)into the space between the shield structure 169 and the vertical piece167. The convex surfaces of the shield structure 169 and vertical piece167 provide for wider points of entry for an engaging member undergoinga lateral relative motion into the space. The convex surfaces of thevertical piece 167 and shield structure 169 include raised portions 171,172, respectively, formed at central portions thereof. The purpose ofportions 171, 172 will be described below.

[0150] A label-receiving structure 174 having a flat label-receivingsurface 175 is provided on an end of the MTU 160 opposite the shieldstructure 169 and MTU manipulating structure 166. Labels, such asscannable bar codes, can be placed on the surface 175 to provideidentifying and instructional information on the MTU 160.

[0151] The MTU 160 preferably includes tiplet holding structures 176adjacent the open mouth of each respective receptacle vessel 162. Eachtiplet holding structure 176 provides a cylindrical orifice within whichis received a contact-limiting tiplet 170. The construction and functionof the tiplet 170 will be described below. Each holding structure 176 isconstructed and arranged to frictionally receive a tiplet 170 in amanner that prevents the tiplet 170 from falling out of the holdingstructure 176 when the MTU 160 is inverted, but permits the tiplet 170to be removed from the holding structure 176 when engaged by a pipette.

[0152] As shown in FIG. 59, the tiplet 170 comprises a generallycylindrical structure having a peripheral rim flange 177 and an uppercollar 178 of generally larger diameter than a lower portion 179 of thetiplet 170. The tiplet 170 is preferably formed from conductivepolypropylene. When the tiplet 170 is inserted into an orifice of aholding structure 176, the flange 177 contacts the top of structure 176and the collar 178 provides a snug but releasable interference fitbetween the tiplet 170 and the holding structure 176.

[0153] An axially extending through-hole 180 passes through the tiplet.Hole 180 includes an outwardly flared end 181 at the top of the tiplet170 which facilitates insertion of a pipette tubular probe (not shown)into the tiplet 170. Two annular ridges 183 line the inner wall of hole180. Ridges 183 provide an interference friction fit between the tiplet170 and a tubular probe inserted into the tiplet 170.

[0154] The bottom end of the tiplet 170 preferably includes a beveledportion 182. When tiplet 170 is used on the end of an aspirator that isinserted to the bottom of a reaction receptacle, such as a receptaclevessel 162 of an MTU 160, the beveled portion 182 prevents a vacuum fromforming between the end of the tiplet 170 and the bottom of the reactionreceptacle vessel.

[0155] Lower Chassis

[0156] An embodiment of the lower chassis of the present invention isshown in FIGS. 52-54. The lower chassis 1100 includes a steel frame 1101with a black polyurethane powder coat, a pull-out drip tray 1102disposed below the chassis, a right-side drawer 1104, and a left-sidedrawer 1106. The left-side drawer 1106 is actually centrally disposedwithin the lower chassis 1100. The far left-side of the lower chassis1100 houses various power supply system components and other analyzermechanisms such as, for example, seven syringe pumps 1152 mounted on amounting platform 1154, a vacuum pump 1162 preferably mounted on thefloor of the lower chassis 1100 on vibration isolators (not shown), apower supply unit 1156, a power filter 1158, and fans 1160.

[0157] A different syringe pump 1152 is designated for each of the fivemagnetic separation wash stations 800, one is designated for theleft-side orbital mixer 552, and one is designated for the deactivationqueue 750. Although syringe pumps are preferred, peristaltic pumps maybe used as an alternative.

[0158] The vacuum pump 1162 services each of the magnetic separationwash stations 800 and the deactivation queue 750. The preferred ratingof the vacuum pump is 5.3-6.5 cfm at 0″ Hg and 4.2-5.2 cfm at 5″ Hg. Apreferred vacuum pump is available from Thomas Industries, Inc. ofSheboygan, Wis., as model number 2750CGHI60. A capacitor 1172 is sold inconjunction with the pump 1162.

[0159] The power supply unit 1156 is preferably an ASTEC, model numberVS1-B5-B7-03, available from ASTEC America, Inc., of Carlsbad, Calif.Power supply unit 1156 accepts 220 volts ranging from 50-60 Hz, i.e.,power from a typical 220 volt wall outlet. Power filter 1158 ispreferably a Corcom model 20MV1 filter, available from Corcom, Inc. ofLibertyville, Ill. Fans 1160 are preferably Whisper XLDC fans availablefrom Comair Rotron, of San Ysidro, Calif. Each fan is powered by a 24VDCmotor and has a 75 cfm output. As shown in FIG. 52, the fans 1160 arepreferably disposed proximate a left-side outer wall of the lowerchassis 1100. The fans 1160 are preferably directed outwardly to drawair through the lower chassis from the right-side thereof to theleft-side thereof, and thus, to draw excess heat out of the lowerchassis.

[0160] Other power supply system components are housed in the backleft-hand side of the lower chassis 1100, including a power switch 1174,preferably an Eaton circuit breaker switch 2-pole, series JA/S,available from the Cutler-Hammer Division of Eaton Corporation ofCleveland, Ohio, and a power inlet module 1176 at which a power cord(not shown) for connecting the analyzer 50 to an external power sourceis connected. The power supply system of the analyzer 50 also includes aterminal block (not shown), for attaching thereto a plurality ofelectrical terminals, a solid state switch (not shown), which ispreferably a Crydom Series 1, model number D2425, available from CalSwitch, Carson City, Calif., for switching between different circuits,and an RS232 9-pin connector port for connecting the analyzer 50 to theexternal computer controller 1100.

[0161] The right-side drawer and left-side drawer bays are preferablyclosed behind one or two doors (not shown) in front of the analyzer,which is/are preferably locked by the assay manager program duringoperation of the analyzer. Microswitches are preferably provided toverify door-closed status. The far left bay is covered by a front panel.End panels are provided on opposite ends of the lower chassis to enclosethe chassis.

[0162] Four leveler feet 1180 extend down from the four corners of thechassis 1100. The leveler feet 1180 include threaded shafts with pads atthe lower ends thereof When the analyzer is in a desired location, thefeet 1180 can be lowered until the pads engage the floor to level andstabilize the analyzer. The feet can also be raised to permit theanalyzer to be moved on its casters.

[0163] Bulk fluids typically contained in the containers of the lowerchassis 1100 may include wash buffer (for washing immobilized target),distilled water (for washing fixed pipette tips), diagnostic testingreagents, silicon oil (used as a floating fluid for layering over testreagents and specimen), and a bleach-based reagent (used for sampledeactivation).

[0164] The right-side drawer 1104 is shown in detail in FIG. 53. Theright-side drawer 1104 includes a box-like drawer structure with a frontdrawer handle 1105. Although drawer handle 1105 is shown as aconventional pull-type drawer handle, in the preferred embodiment of theanalyzer 50, handle 1105 is a T-handle latch, such as those availablefrom Southco, Inc. of Concordville, Pa. The drawer 1104 is mounted inthe lower chassis on slide brackets (not shown) so that the drawer 1104can be pulled into and out of the lower chassis. A sensor (not shown) ispreferably provided for verifying that the drawer 1104 is closed. Thefront portion of the drawer includes bottle receptacles 1122 for holdingbottle 1128 (shown in FIG. 52), which is a dedicated pipette washwaste-containing bottle, and bottle 1130 (also shown in FIG. 52), whichis a dedicated waste bottle for containing waste from a magnetic wash,target-capture procedure. Bottle 1130 is preferably evacuated.

[0165] The analyzer 50 will not begin processing assays if any of thebottles required in the lower chassis 1100 are missing. Bottlereceptacles 1122 preferably include bottle-present sensors (not shown)to verify the presence of a bottle in each receptacle 1122. Thebottle-present sensors are preferably diffuse reflective type opticalsensors available from SUNX/Ramco Electric, Inc., of West Des Moines,Iowa, model EX-14A.

[0166] Right-side drawer 1104 further includes a waste bin 1108 forholding therein spent MTUs and specimen tips. Waste bin 1108 is an openbox structure with a sensor mount 1112 at a top portion thereof formounting thereon a sensor, preferably a 24VDC Opto-diffuse reflectorswitch (not shown), for detecting whether the waste bin 1108 is full.Another diffuse reflector type optical sensor (not shown) is positionedwithin right-side drawer 1104 to verify that the waste bin 1108 is inplace. Again, diffuse reflective type optical sensors available fromSUNX/Ramco Electric, Inc., of West Des Moines, Iowa, model EX-14A, arepreferred.

[0167] A deflector 1110 extends obliquely from a side of the waste bin1108. Deflector 1110 is disposed directly below a chute through whichspent MTUs are dropped into the waste bin 1108 and deflects the droppedMTUs toward the middle of the waste bin 1108 to avoid MTU pile-ups in acorner of the waste bin 1108. Deflector 1110 is preferably pivotallymounted so that it can pivot upwardly to a substantially verticalposition so that when a waste bag, which lines the waste bin 1108 andcovers the deflector 1110, is removed from the waste bin 1108, thedeflector 1110 will pivot upwardly with the bag as it is pulled out andtherefore will not rip the bag.

[0168] A printed circuit board (not shown) and cover 1114 can be mountedto the front of the waste bin 1108. Sensor mounts 1116 and 1117 are alsomounted to the front of waste bin 1108. Sensors 1118 and 1119 aremounted on sensor mount 1116, and sensors 1120 and 1121 mounted onsensor mount 1117. Sensors 1118, 1119, 1120, and 1121 are preferably DCcapacitive proximity sensors. The upper sensors 1118, 1119 indicate whenthe bottles 1128 and 1130 are full, and the bottom sensors 1120, 1121indicate when the bottles are empty. Sensors 1118-1121 are preferablythose available from Stedham Electronics Corporation of Reno, Nev.,model number C2D45AN1-P, which were chosen because their relatively flatphysical profile requires less space within the tight confines of thelower chassis 1100 and because the Stedham sensors provide the desiredsensing distance range of 3-20 mm.

[0169] The analyzer 50 will preferably not begin performing any assaysif the assay manager program detects that any of the waste fluidcontainers in the right-side drawer 1104 are not initially empty.

[0170] The capacitive proximity sensors 1118-1121 and thebottle-present, waste-bin-present, and waste-bin-full optical sensors ofthe right-side drawer 1104 are connected to the printed circuit board(not shown) behind cover 1114, and the printed circuit board isconnected to the embedded controller of the analyzer 50.

[0171] Because the right-side drawer 1104 cannot be pulled completelyout of the lower chassis 1100, it is necessary to be able to pull thewaste bin 1108 forward so as to permit access to the waste bin forinstalling and removing a waste bag liner. For this purpose, a handle1126 is mounted to the front of the waste bin 1108 and teflon strips1124 are disposed on the bottom floor of the right-side drawer 1104 tofacilitate forward and backward sliding of the waste bin 1108 in thedrawer 1104 when bottles 1128 and 1130 are removed.

[0172] Details of the left-side drawer 1106 are shown in FIG. 54.Left-side drawer 1106 includes a box-like structure with a front mountedhandle 1107 and is mounted within the lower chassis 1100 on slidebrackets (not shown). Although handle 1107 is shown as a conventionalpull-type drawer handle, in the preferred embodiment of the analyzer 50,handle 1107 is a T-handle latch, such as those available from Southco,Inc. of Concordville, Pa. A sensor is provided for verifying that theleft-side drawer 1106 is closed.

[0173] Left-side drawer 1106 includes a tiplet waste bin 1134 with amounting structure 1135 for mounting thereon a tiplet-waste-bin-fullsensor (not shown). A tiplet-waste-bin-present sensor is preferablyprovided in the left-side drawer 1106 to verify that the tiplet wastebin 1134 is properly installed. Diffuse reflective type optical sensorsavailable from SUNX/Ramco Electric, Inc., of West Des Moines, Iowa,model EX-14A, are preferred for both the tiplet-waste-bin-full sensorand the tiplet-waste-bin-present sensor.

[0174] Bundling structures 1132 are provided for securing and bundlingvarious tubing and/or wires (not shown) within the lower chassis 1100.The bundling structures preferably used are Energy Chain Systemsmanufactured and sold by Igus, Inc. of East Providence, R.I.

[0175] A printed circuit board 1182 is mounted behind a panel 1184 whichis located behind the tiplet waste bin 1134. A solenoid valve mountingpanel 1186 is located below the tiplet waste bin 1134.

[0176] Left-side drawer 1106 includes a forward container-holdingstructure for holding therein six similarly sized bottles. The containerstructure includes divider walls 1153, 1155, 1157, and 1159 andcontainer blocks 1151 having a curved bottle-conforming front edge,which together define six container-holding areas. Lower sensors 1148and upper sensors 1150 (six of each) are mounted on the divider walls1155, 1157, and 1159. The upper and lower sensors 1148, 1150 arepreferably DC capacitive proximity sensors (preferably sensors availablefrom Stedham Electronics Corporation of Reno, Nev., model numberC2D45AN1-P, chosen for their flat profile and sensing range). The uppersensors 1150 indicate when the bottles held in the container structureare full, and the lower sensors 1148 indicate when the bottles areempty. In the preferred arrangement, the left two bottles 1146 contain adetecting agent (“Detect I”), the middle two bottles 1168 containsilicon oil, and the right two bottles 1170 contain another detectingagent (“Detect II”).

[0177] Bottle-present sensors (not shown) are preferably provided ineach of the container-holding areas defined by the container blocks 1151and the dividing walls 1153, 1155, 1157, and 1159 to verify the presenceof bottles in each container-holding area. The bottle-present sensorsare preferably diffuse reflective type optical sensors available fromSUNX/Ramco Electric, Inc., of West Des Moines, Iowa, model EX-14A.

[0178] A large centrally located container receptacle 1164 holds abottle 1140 (shown in FIG. 52), preferably containing deionized water.Container receptacles 1166 (only one is visible in FIG. 54) hold bottles1142 and 1144 (also shown in FIG. 52) preferably containing a washbuffer solution. A dividing wall 1143 between the receptacle 1164 and1166 has mounted thereon sensors, such as sensor 1141, for monitoringthe fluid level in the bottles 1140, 1142, and 1144. The sensors, suchas sensor 1141, are preferably DC capacitive proximity sensors(preferably sensors available from Stedham Electronics Corporation ofReno, Nev., model number C2D45AN1-P).

[0179] Container receptacles 1164 and 1166 preferably includebottle-present sensors (not shown) for verifying that bottles areproperly positioned in their respective receptacles. The bottle-presentsensors are preferably diffuse reflective type optical sensors availablefrom SUNX/Ramco Electric, Inc., of West Des Moines, Iowa, model EX-14A.

[0180] The analyzer 50 will not begin performing any assays if the assaymanager program determines that any of the bulk-fluid containers in theleft-side drawer 1106 are initially empty.

[0181] The capacitive proximity fluid level sensors, the variousbottle-present sensors, the tiplet-waste-bin-full sensor, and thetiplet-waste-bin-present sensors are all connected to the printedcircuit board 1182, and the printed circuit board 1182 is connected tothe embedded controller of the analyzer 50.

[0182] Four solenoid valves (not shown) are mounted below the solenoidvalve mounting panel 1186. The solenoid valves connect bulk fluidbottles where fluids are stored in pairs of bottles, i.e., the bottles1140, 1142 containing wash buffer solution, the two bottles 1146containing the “Detect I” agent, the two bottles 1168 containing oil,and the two bottles 1170 containing the “Detect II” agent. The solenoidvalves, in response to signals from the respective capacitive proximitysensors, switch bottles from which fluid is being drawing when one ofthe two bottles containing the same fluid is empty. In addition, thesolenoid valves may switch bottles after a prescribed number of testsare performed. The preferred solenoid valves are teflon solenoid valvesavailable from Beco Manufacturing Co., Inc. of Laguna Hills, Calif.,model numbers S313W2DFRT and M223W2DFRLT. The two different modelnumbers correspond to solenoid valves adapted for use with two differenttube sizes. Teflon solenoid valves are preferred because they are lesslikely to contaminate fluids flowing through the valves and the valvesare not damaged by corrosive fluids flowing through them.

[0183] Bottle 1136 (see FIG. 52) is a vacuum trap held in a vacuum trapbracket 1137, and bottle 1138 contains a deactivating agent, such asbleach-containing reagent. Again, bottle-present sensors are preferablyprovided to verify the presence of bottles 1136 and 1138.

[0184] A hand-held bar code scanner 1190 may be provided in the lowerchassis 1100 for scanning information provided on scannable containerlabels into the assay manager program. Scanner 1190 is connected by acord to printed circuit board 1182 of the left-side drawer 1106 and ispreferably stowed on a bracket (not show) mounted on dividing wall 1143.Scanners available from Symbol Technologies, Inc., of Holtsville, N.Y.,series LS2100, are preferred.

[0185] Specimen Ring and Specimen Tube Trays

[0186] Specimens are contained in the specimen tubes 320, and the tubes320 are loaded into the tube trays 300 outside the analyzer 50. Thetrays 300 carrying the specimen tubes 320 are placed onto the specimenring 250 through the access opening provided by opening the flip-upcarousel door 80.

[0187] Referring to FIGS. 5 and 6, the first ring assembly, or specimenring, 250 is formed of milled, unhardened aluminum and includes a raisedring structure defining an annular trough 251 about the outer peripheryof ring 250 with a plurality of raised, radially extending dividers 254extending through trough 251. Preferably, nine dividers 254 divide thetrough 251 into nine arcuate specimen tube tray-receiving wells 256. Thetrough 251 and wells 256 define an annular fluid container carrierportion constructed and arranged to carry a plurality of containers aswill be described below.

[0188] Specimen ring 250 is preferably rotationally supported by three120°-spaced V-groove rollers 257, 258, 260 which engage a continuousV-ridge 262 formed on the inner periphery of ring 250, as shown in FIGS.5, 6, and 6A so that the ring 250 is rotatable about a first centralaxis of rotation. The rollers are preferably made by Bishop-WisecarverCorp. of Pittsburg, Calif., model number W1SSX. Rollers 257 and 260 arerotationally mounted on fixed shafts, and roller 258 is mounted on abracket which pivots about a vertical axis and is spring biased so as tourge roller 258 radially outward against the inner periphery of ring250. Having two fixed rollers and one radially movable roller allows thethree rollers to accommodate an out-of-round inner periphery of the ring250.

[0189] Specimen ring 250 is driven by stepper motor 264 (VEXTA steppermotors available from Oriental Motor Co., Ltd. of Tokyo, Japan as modelnumber PK266-01A are preferred) via continuous belt 270 (preferablyavailable from SDP/SI of New Hyde Park, N.Y., as model numberA6R3M444080) which extends over guide rollers 266, 268 and around theouter periphery of ring 250. A home sensor and a sector sensor (notshown), preferably slotted optical sensors, are provided adjacent thering 250 at a rotational home position and at a position correspondingto one of the specimen tube tray receiving wells 256. The ring 250includes a home flag (not shown) located at a home position on the wheeland nine equally-spaced sector flags (not shown) corresponding to thepositions of each of the nine specimen tube tray receiving wells 256.The home flag and sector flags cooperate with the home sensor and sectorsensors to provide ring position information to the assay managerprogram and to control the ring 250 to stop at nine discrete positionscorresponding to established coordinates for user re-load and access bypipette unit 450. Preferred sensors for the home sensor and sectorsensor are Optek slotted optical sensors, model number OPB857, availablefrom Optek of Carrollton, Tex.

[0190] A specimen cover is disposed over a portion of the annular fluidcontainer carrier portion, or trough 251, and comprises an arcuate coverplate 138 fixed in an elevated position with respect to the wheel 250 onthree mounting posts 136. Plate 138 has an arcuate shape generallyconforming to the curve of the trough 251. A first opening 142 is formedin the plate 138, and a second opening 140 is formed in the plate 138 ata greater radial distance from the axis of rotation of ring 250 thanopening 142 and at a circumferentially-spaced position from opening 142.

[0191] Referring to FIGS. 55-57, each specimen tube tray 300 comprises atest tube rack structure that is curved to conform to the curvature ofthe ring 250. Each tray 300 comprises a central wall structure 304 withlateral end walls 303 and 305 disposed on either end of wall 304. Afloor 312 extends across the bottom of the tray 300. The principlepurposes of specimen tube tray 300 are to hold specimen tubes on thespecimen ring 250 for access by the specimen pipette assembly 450 and tofacilitate loading and unloading of multiple specimen tubes into andfrom the analyzer.

[0192] A plurality of Y-shaped dividers 302 are equidistantly spacedalong opposite edges of the tray 300. Each two adjacent dividers 302define a test-tube receiving area 330. End wall 303 includes inwardlybent flanges 316 and 318, and end wall 305 includes inwardly bentflanges 326 and 328. The respective inwardly bent flanges of end walls303 and 305 along with the end-most of the dividers 302 define theend-most tube receiving areas 332. The receiving areas 330, 332 arearcuately aligned along two arcuate rows on opposite sides of centralwall structure 304.

[0193] Referring to FIG. 57, within each tube receiving area 330, 332, aleaf spring element 310 is attached to central wall 304. Leaf springelement 310, preferably formed of stainless spring steel, elasticallydeflects when a test tube 320 is inserted into the tube-receiving area330 or 332 and urges the tube 320 outwardly against the dividers 302.Thus, the tube 320 is secured in an upright orientation. The shape ofthe dividers 302 and the elasticity of the leaf spring elements 310allow the tray 300 to accommodate specimen tubes of various shapes andsizes, such as tubes 320 and 324. Each tray 300 preferably includes ninedividers 302 along each edge to form, along with end walls 303 and 305,ten tube-receiving areas 330, 332 on each side of central wall structure304 for a total of twenty tube-receiving areas per tray. Indicia fordesignating tube-receiving areas 330 and 332, such as raised numerals306, may be provided on the tray, such as on central wall 304.

[0194] Each tray 300 may also include boss structures 308, shown in theillustrated embodiment to be integrally formed with the end-mostdividers 302. An upright inverted U-shaped handle (not shown) may beattached to the tray at boss structures 308 or some other suitablelocation. Upright handles can facilitate handling of the tray 300 whenloading and unloading the tray 300 through the arcuate carousel door 80,but are not necessarily preferred.

[0195] A gap is provided between adjacent dividers 302 so that bar-codelabels 334, or other readable or scannable information, on the tubes 320is accessible when the tube is placed in the tray 300. When a tray 300carried on wheel 250 passes beneath the plate 138 of the specimen cover,one tube 320 in a curved row at a radially-inward position with respectto wall structure 304 will be aligned with first opening 142 and anothertube 320 in a curved row at a radially-outward position with respect towall 304 will be aligned with second opening 140. The ring 250 isindexed to sequentially move each tube 320 beneath the openings 140, 142to permit access to the tubes.

[0196] Referring again to FIG. 5, bar code scanners 272 and 274 aredisposed adjacent the ring 250. Opticon, Inc. scanners, model numberLHA2126RR1S-032, available from Opticon, Inc. of Orangeburg, N.Y., arepreferred. Scanner 272 is located outside ring 250, and scanner 274 isdisposed inside ring 250. Scanners 272 and 274 are positioned to scanbar code data labels on each specimen tube 320 carried in the specimentube tray 300 as the ring 250 rotates a tray 300 of specimen tubes 320past the scanners 272, 274. In addition, the scanners 272, 274 scan thebar code label 337 (see FIG. 55) on the outer portion of bent flanges316 and 31100of end wall 303 of each tray 300 as the tray 300 is broughtinto the specimen preparation area. Various information, such asspecimen and assay identification, can be placed on the tubes and/oreach tray 300, and this information can be scanned by the scanners 272,274 and stored in the central processing computer. If no specimen tubeis present, the tray 300 presents a special code 335 (see FIG. 55) to beread by the scanners 272, 274.

[0197] Ipette Tip Wheel

[0198] As shown primarily in FIGS. 5 and 6, a second ring assembly ofthe preferred embodiment is a pipette tip wheel 350 and comprises acircular ring 352 at a bottom portion thereof, a top panel 374 defininga circular inner periphery and five circumferentially-spaced,radially-protruding sections 370, and a plurality of generallyrectangular risers 354 separating the top panel 374 from the ring 352and preferably held in place by mechanical fasteners 356 extendingthrough the top panel 374 and ring 352 into the risers 354. Fiverectangular openings 358 are formed in the top panel 374 proximate eachof the sections 370, and a rectangular box 376 is disposed beneath panel374, one at each opening 358. Top panel 374, ring 352, and risers 354are preferably made from machined aluminum, and boxes 376 are preferablyformed from stainless steel sheet stock.

[0199] The openings 358 and associated boxes 376 are constructed andarranged to receive trays 372 holding a plurality of disposable pipettetips. The pipette tip trays 372 are preferably those manufactured andsold by TECAN (TECAN U.S. Inc., Research Triangle Park, N.C.) under thetrade name “Disposable Tips for GENESIS Series”. Each tip has a 1000 μlcapacity and is conductive. Each tray holds ninety-six elongateddisposable tips.

[0200] Lateral slots 378 and longitudinal slots 380 are formed in thetop panel 374 along the lateral and longitudinal edges, respectively, ofeach opening 358. The slots 378, 380 receive downwardly-extendingflanges (not shown) disposed along the lateral and longitudinal edges ofthe trays 372. The slots 378, 380 and associated flanges of the trays372 serve to properly register the trays 372 with respect to openings358 and to hold the trays 372 in place on the panel 374.

[0201] Pipette tip wheel 350 is preferably rotationally supported bythree 120°-spaced V-groove rollers 357, 360, 361 which engage acontinuous V-ridge 362 formed on the inner periphery of ring 352, asshown in FIGS. 5, 6, and 6A, so that the pipette tip wheel 350 isrotatable about a second central axis of rotation that is generallyparallel to the first axis of rotation of the specimen ring 250. Therollers are preferably made by Bishop-Wisecarver Corp. of Pittsburg,Calif., model number W1SSX. Rollers 357 and 360 are rotationally mountedon fixed shafts, and roller 361 is mounted on a bracket which pivotsabout a vertical axis and is spring biased so as to urge roller 361radially outwardly against the inner periphery of ring 352. Having twofixed rollers and one radially movable roller allows the three rollersto accommodate an out-of-round inner periphery of ring 352. In addition,the wheel 350 can be easily installed and removed by merely pushingpivoting roller 361 radially inwardly to allow the ring 352 to movelaterally to disengage continuous V-ridge 362 from the fixed V-grooverollers 357, 360.

[0202] Pipette tip wheel 350 is driven by a motor 364 having ashaft-mounted spur gear which meshes with mating gear teeth formed on anouter perimeter of ring 352. Motor 364 is preferably a VEXTA gear headstepper motor, model number PK243-A1-SG7.2, having a 7.2:1 gearreduction and available from Oriental Motor Co., Ltd. of Tokyo, Japan. Agear head stepper motor with a 7.2:1 gear reduction is preferred becauseit provides smooth motion of the pipette tip wheel 350, where the spurgear of the motor 364 is directly engaged with the ring 352.

[0203] A home sensor and a sector sensor (not shown), preferably slottedoptical sensors, are provided adjacent the pipette tip wheel 350 at arotational home position and at a position of one of the boxes 376. Thepipette tip wheel 350 includes a home flag (not shown) located at a homeposition on the wheel and five equally-spaced sector flags (not shown)corresponding to the positions of each of the five boxes 376. The homeflag and sector flags cooperate with the home sensor and sector sensorsto provide wheel position information to the assay manager program andto control the pipette tip wheel 350 to stop at five discrete positionscorresponding to established coordinates for user re-load and access bypipette unit 450. Preferred sensors for the home sensor and sectorsensor are Optek Technology, Inc. slotted optical sensors, model numberOPB980, available from Optek Technology, Inc. of Carrollton, Tex.

[0204] Multi-axis Mixer

[0205] Referring to FIGS. 7-12, the multi-axis mixer 400 includes arotating turntable structure 414 (see FIG. 10) rotatably mounted on acenter shaft 428 supported in center bearings 430 to a fixed base 402mounted to the jig plate 130 by means of mechanical fasteners (notshown) extending through apertures 419 formed about the outer peripheryof the fixed base 402. A cover member 404 is attached to and rotateswith turntable 414.

[0206] Turntable 414 is preferably in the form of a right angle crosscomprising three 90°-spaced rectangular arms 444 of equal lengthextending radially outwardly from the center of the turntable 414 and afourth arm 445 having an extension 417 making arm 445 slightly longerthan arms 444. As shown in FIGS. 10-12, the center portion of turntable414 is connected to center shaft 428 by a screw 429.

[0207] Four container holders 406 are disposed on the ends of the arms444 and 445 of turntable frame 414. Each container holder 406 isattached to one of four vertical shafts 423, which are rotatablysupported in container holder bearings 415. Container holder bearings415 are pressed into the arms 444, 445 of the turntable 414 and aredisposed at equal radial distances from shaft 428.

[0208] The cover member 404 includes four circular openings withupwardly-turned peripheral flanges 401 through which shafts 423 extend.Upward flanges 401 can advantageously prevent spilled liquids fromflowing into the openings.

[0209] The container holders 406 comprise generally cylindrical membershaving an open bottom and an open top for receiving and holding acontainer 440, preferably a plastic bottle, of target capture reagent.

[0210] The target capture reagent used with the preferred assay includesmagnetically responsive particles with immobilized polynucleotides,polynucleotide capture probes, and reagents sufficient to lyse cellscontaining the targeted nucleic acids. After cell lysis, targetednucleic acids are available for hybridization under a first set ofpredetermined hybridization conditions with one or more capture probes,with each capture probe having a nucleotide base sequence region whichis capable of hybridizing to a nucleotide base sequence region containedon at least one of the targeted nucleic acids. Under a second set ofpredetermined hybridization conditions, a homopolymer tail (e.g.,oligo(dT)) of the immobilized polynucleotides is capable of hybridizingwith a complementary homopolymer tail (e.g., oligo(dA)) contained on thecapture probe, thereby immobilizing targeted nucleic acids.Target-capture methods and lysing procedures are well known in the artand are described more fully in the background section supra.

[0211] A container retainer spring 408 spans a lateral slot formed inthe wall of each container holder 406 and helps to hold the container440 within the container holder 406 by urging the container 440 toward aportion of the inner peripheral wall of the holder 406 opposite thespring 408.

[0212] Each container holder 406 is secured to an associated verticalshaft 423 by a shaft block structure 432. Shaft block structure 432includes curved end portions which conform to the inside of thecylindrical container holder 406, and the container holder 406 issecured to the block 432 by fasteners 434. A generally circular aperture449 receives the shaft 423. A slot 438 extends from aperture 449 to anend of the block 432 which does not extend all the way to the inside ofthe container holder 406, and a second slot 436 extends from an edge ofthe block 432 generally perpendicularly to slot 438 so as to define acantilevered arm 435. A machine screw 437 extends through a through-hole441 formed laterally through block 432 and into a threaded hole 447formed laterally through arm 435. As screw 437 is tightened, arm 435deflects, thus tightening aperture 449 around shaft 423.

[0213] The shaft block structure 432, the shaft 423, and the containerholder bearings 415 associated with each container holder 406 define apreferred container holder mounting structure associated with eachcontainer holder 406 that is constructed and arranged to mount thecontainer holder 406 to the turntable 414 and permit the containerholder 406 to rotate about an axis of rotation 412 of the shaft 423.

[0214] Container holder planetary gears 422 are attached to the oppositeends of shafts 423. The planetary gears 422 operatively engage astationary sun gear 416. A drive pulley 418 is attached to center shaft428 and is coupled to a drive motor 420 by a drive belt (not shown).Drive motor 420 is preferably mounted so as to extend through an opening(not shown) in the jig plate 130 below the base 402. Drive motor 420 ispreferably a stepper motor, and most preferably a VEXTA stepper motor,model number PK264-01A, available from Oriental Motor Co., Ltd. ofTokyo, Japan. The drive motor 420, via the drive belt and drive pulley418, rotates the center shaft 428 and the turntable 414 attachedthereto. As the turntable frame 414 rotates about the center line ofcenter shaft 428, the planetary gears 422 engaged with sun gear 416cause the shafts 423 and container holders 406 attached thereto torotate at the ends of the arms 444 of the turntable frame 414. Eachcontainer holder 406 is preferably mounted such that the axis ofrotation 410 thereof is offset from the axis of rotation 412 of theassociated shaft 423. Thus, each container holder 406 rotateseccentrically about axis 412 of the associated shaft 423. Accordingly,the planetary gears 422 and the sun gear 416 constitute rotationalmotion coupling elements constructed and arranged to cause the containerholders 406 to rotate about the respective axes of rotation of theshafts 423 as the turntable 414 rotates about the axis of rotation ofthe shaft 428.

[0215] A bar code scanner device 405 is preferably mounted on a bracket403 and reads bar code information of the containers 440 through ascanner slot 407 formed in each container holder 406. The preferredscanner is a model number NFT1125/002RL scanner, available from Opticon,Inc. of Orangeburg, N.Y.

[0216] The multi-axis mixer 400 usually rotates during operation of theanalyzer 50 to agitate the fluid contents of the containers 440 tothereby keep the target capture reagent in suspension, stopping onlybriefly to permit pipette unit 456 to withdraw an amount of mixture fromone of the containers. Pipette unit 456 draws mixture from a bottle atthe same location each time. Therefore, it is desirable to monitor thepositions of the bottles so that the bottle from which mixture iswithdrawn each time can be specified.

[0217] Four optical slotted sensors 426, each comprising an opticalemitter and detector, are stationed around the periphery of fixed base402, spaced at 90° intervals. Optical sensors available from OptekTechnology, Inc. of Carrollton, Tex., model number OPB490P 11, arepreferred. A sensor tab 424 extends down from extension 417 at the endof arm 445 of the turntable 414. When sensor tab 424 passes through asensor 426, the communication between the emitter and detector is brokenthus giving a “container present” signal. The tab 424 is only providedat one location, e.g., the first container location. By knowing theposition of the first container, the positions of the remainingcontainers, which are fixed relative to the first container, are alsoknown.

[0218] Power and control signals are provided to the multi-axis mixer400 via a power and data connector. While the multi-axis mixer 400provides mixing by rotation and eccentric revolution, other mixingtechniques, such as vibration, inversion, etc. may be used.

[0219] Specimen Preparation Procedure

[0220] To begin specimen preparation, the pipette unit 456 moves totransfer target capture reagent, preferably mag-oligo reagent, from acontainer 440 carried on the multi-axis mixer 400 into each of thereceptacle vessels 162 of the MTU 160. The target capture reagentincludes a support material able to bind to and immobilize a targetanalyte. The support material preferably comprises magneticallyresponsive particles. At the beginning of the specimen preparationprocedure, the pipette unit 456 of the right-side pipette assembly 450moves laterally and longitudinally to a position in which the probe 457is operatively positioned over a pipette tip in one of the trays 372.

[0221] The tip trays 372 are carried on the pipette tip wheel 350 so asto be precisely positioned to achieve proper registration between thepipette tips and the tubular probe 457 of the pipette unit 456. Thepipette unit 456 moves down to insert the free end of the tubular probe457 into the open end of a pipette tip and frictionally engage thepipette tip. The Cavro processors preferably used for pipette unit 456includes a collar (not shown), which is unique to Cavro processors. Thiscollar is moved slightly upwardly when a pipette tip is frictionallyengaged onto the end of the tubular probe 457, and the displaced collartrips an electrical switch on the pipette unit 456 to verify that apipette tip is present. If tip pick-up is not successful (e.g., due tomissing tips in the trays 372 or a misalignment), a missing tip signalis generated and the pipette unit 456 can move to retry tip engagementat a different tip location.

[0222] The assay manager program causes the multi-axis mixer 400 tobriefly stop rotating so that the pipette unit 456 can be moved to aposition with the tubular probe 457 and attached pipette tip of thepipette unit 456 aligned over one of the stationary containers 440. Thepipette unit 456 lowers the pipette tip attached to the tubular probe457 into the container 440 and draws a desired amount of target capturereagent into the pipette tip. The pipette unit 456 then moves the probe457 out of the container 440, the multi-axis mixer 400 resumes rotating,and the pipette unit 456 moves to a position above opening 252 and thespecimen transfer station 255. Next, the pipette unit 456 descends,moving the pipette tip and the tubular probe 457 through the opening252, and dispenses a required amount of target capture (typically100-500 μl) into one or more of the receptacle vessels 162 of the MTU160. It is preferred that the target capture reagent is drawn only intothe pipette tip and not into the probe 457 itself Furthermore, it ispreferred that the pipette tip be of sufficient volumetric capacity tohold enough reagent for all five vessels 162 of the MTU 160.

[0223] After target capture reagent transfer, the pipette unit 456 thenmoves to a “tip discard” position above tip disposal tube 342, where thedisposable pipette tip is pushed or ejected off of the end of thetubular probe 457 of the pipette unit 456, and falls through tube 342toward a solid waste container. An optical sensor (not shown) isdisposed adjacent to tube 342, and before tip discard, the specimenpipette assembly 450 moves the pipette unit 456 into a sensing positionof the sensor. The sensor detects whether a tip is engaged with the endof the tubular probe 457 to verify that the tip is still held on thetubular probe 457 of the pipette unit 456, thereby confirming that thetip was on the tubular probe 457 throughout specimen preparation. Apreferred sensor is a wide-gap slotted optic sensor, model OPB900W,available from Optek Technology, Inc. of Carrollton, Tex.

[0224] Preferably, the pipette tip is ejected by the collar (not shown)on the tubular probe 457 of pipette unit 456. The collar engages a hardstop when the tubular probe 457 is raised, so that as the probe 457continues to ascend, the collar remains fixed and engages an upper endof the pipette tip, thereby forcing it off the tubular probe 457.

[0225] After pipetting the target capture and discarding the pipettetip, the probe 457 of the pipette unit 456 can be washed by runningdistilled water through the tubular probe 457 at the tip wash stationbasin 346. The tip wash water is collected and drains down into a liquidwaste container.

[0226] Following the reagent dispensing procedure, the pipette unit 456on the right pipette assembly 450 moves laterally and longitudinally toa position in which the tubular probe 457 of the pipette unit 456 iscentered over a new pipette tip on one of the tip trays 372. Aftersuccessful tip engagement, the pipette unit 456 moves back over thespecimen ring 250, adjacent to the specimen preparation opening 252 andwithdraws a test specimen (about 25-900 μl) from a specimen tube 320that is aligned with one of the openings 140, 142 of the cover plate138. Note that both openings 140, 142 include upwardly extendingperipheral flanges to prevent any fluids spilled onto the plate 138 fromrunning into the openings 140, 142. The pipette unit 456 then moves overthe MTU 160 in the specimen transfer station 255, moves down throughopening 252, and dispenses test specimen into one of the receptaclevessels 162 of the MTU 160 containing target capture reagent. Pipetteunit 456 then moves to the “tip discard” position above the tip disposaltube 342, and the disposable pipette tip is ejected into the tube 342.Pipette unit 456 then picks up a new disposable pipette tip from thepipette tip wheel 350, the specimen ring 250 indexes so that a newspecimen tube is accessible by the pipette unit 456, unit 456 moves toand draws specimen fluid from the specimen tube into the disposablepipette tip, the pipette unit 456 then moves to a position above thespecimen transfer station 255, and dispenses specimen fluid into adifferent receptacle vessel 162 containing target capture reagent. Thisprocess is preferably repeated until all five receptacle vessels 162contain a combination of fluid specimen sample and target capturereagent.

[0227] Alternatively, depending on the assay protocol or protocols to berun by the analyzer 50, the pipette unit 456 may dispense the same testspecimen material into two or more of the receptacle vessels 162 and theanalyzer can perform the same or different assays on each of thosealiquots.

[0228] As described above with respect to pipette units 480, 482,pipette unit 456 also includes capacitive level sensing capability. Thepipette tips used on the end of the tubular probe 457 are preferablymade from a conductive material, so that capacitive level sensing can beperformed with the pipette unit 456, even when a tip is carried on theend of the tubular probe 457. After the pipette unit has completed atest specimen dispensing procedure, the pipette unit 456 moves thetubular probe 457 back down into the receptacle vessel 162 until the topof the fluid level is detected by the change in capacitance. Thevertical position of the tubular probe 457 is noted to determine whetherthe proper amount of fluid material is contained in the receptaclevessel 162. Lack of sufficient material in a receptacle vessel 162 canbe caused by clotting in the test specimen, which can clot the tip atthe end of the tubular probe 457 and prevent proper aspiration of testspecimen material into the tip and/or can prevent proper dispensing oftest specimen from the tip.

[0229] After specimen transfer, the pipette tip is discarded into thetip disposal tube 342 as described above. Again, the tubular probe 457of the pipette of unit can be washed with distilled water if desired,but washing of the probe is typically not necessary because, in thepreferred method of operation, specimen material only comes into contactwith the disposable pipette tip.

[0230] The assay manager program includes pipette unit control logicwhich controls movements of the pipette units 456, 480, 482, andpreferably causes pipette unit 456 to move in such a manner that itnever passes over a specimen tube 320 on the specimen ring 250, exceptwhen the pipette unit 456 positions the tubular probe 457 over aspecimen tube 320 to withdraw a test specimen or when the specimen tube320 is below the plate 138 of the specimen cover. In this way,inadvertent fluid drips from the tubular probe 457 of the pipette unit450 into another specimen tube, which might result incross-contamination, are avoided.

[0231] Following specimen preparation, the MTU 160 is moved by theright-side transport mechanism 500 from the specimen transfer station tothe right orbital mixer 550 in which the specimen/reagent mixtures aremixed. The structure and operation of the orbital mixers 550, 552 willbe described in further detail below.

[0232] After the MTU 160 is withdrawn from the specimen transfer stationby the right-side transport mechanism 500, the reaction receptacleshuttle assembly within the input queue 150 advances the next MTU into aposition to be retrieved by the right-side transport mechanism 500 whichmoves the next MTU to the specimen transfer station. Specimenpreparation procedures are then repeated for this next MTU.

[0233] Transport Mechanisms

[0234] The right-side and left-side transport mechanisms 500, 502 willnow be described in detail. Referring to FIGS. 13-16, the right-sidetransport mechanism 500 (as well as the left-side transport mechanism502) has a manipulating hook member that, in the illustrated embodiment,includes an extendible distributor hook 506 extending from a hookmounting structure 508 that is radially and slidably displaceable in aslot 510 on a plate 512. A housing 504 on top of the plate 512 has anopening 505 configured to receive the upper portion of an MTU 160. Astepper motor 514 mounted on the plate 512 turns a threaded shaft 516,which, in cooperation with a lead screw mechanism, moves the distributorhook 506 from the extended position shown in FIGS. 13 and 15, to theretracted position shown in FIG. 14, the motor 514 and threaded shaft516 constituting elements of a preferred hook member drive assembly.Stepper motor 514 is preferably a modified HSI, series 46000. HSIstepper motors are available from Haydon Switch and Instrument, Inc. ofWaterbury, Conn. The HSI motor is modified by machining the threads offone end of the threaded shaft 516, so that the shaft 516 can receive thehook mounting structure 508.

[0235] The housing 504, motor 514, and the plate 512 are preferablycovered by a conforming shroud 507.

[0236] As shown in FIG. 16, a stepper motor 51100turns a pulley 520 viaa belt 519. (VEXTA stepper motors, model number PK264-01A, availablefrom Oriental Motor Co., Ltd. of Tokyo, Japan, and SDP timing belts,model number A6R51M200060, available from SDP/SI of New Hyde Park, N.Y.,are preferred). Pulley 520 is preferably a custom-made pulley with onehundred sixty-two (162) axial grooves disposed around its perimeter. Amain shaft 522 fixedly attached to the plate 512, by means of auniquely-shaped mounting block 523, extends down through a base 524 andis fixed to the pulley 520. Base 524 is mounted to the datum plate 82 bymeans of mechanical fasteners extending through apertures 525 formedabout the outer periphery of the base 524. A flex circuit 526 providespower and control signals to the hook mounting structure 508 and motor514, while allowing the plate 512 (and the components carried on theplate) to pivot sufficiently so as to rotate as much as 340° withrespect to the base 524. The transport mechanism 500, 502, assemblypreferably includes hard stops (not shown) at either end of the unit'srotational path of travel.

[0237] An arm position encoder 531 is preferably mounted on an end ofthe main shaft 522. The arm position encoder is preferably an absoluteencoder. A2 series encoders from U.S. Digital in Seattle, Wash., modelnumber A2-S-K-315-H, are preferred.

[0238] The assay manager program provides control signals to the motors518 and 514, and to the hook mounting structure 508, to command thedistributor hook 506 to engage the MTU manipulating structure 166 on MTU160. With the hook 506 engaged, the motor 514 can be energized to rotatethe shaft 516 and thereby withdraw the hook 506, and the MTU 160, backinto the housing 504. The MTU 160 is securely held by the transportmechanism 500, 502 via the sliding engagement of the connecting ribstructure 164 of the MTU 160 with opposed edges 511 of plate 512adjacent slot 510. The plate 512 thereby constitutes an element of apreferred receptacle carrier assembly that is constructed and arrangedto be rotatable about an axis of rotation (e.g., the axis of shaft 522)and to receive and carry a reaction receptacle (e.g., MTU 160). Themotor 518 can rotate the pulley 520 and shaft 522 via the belt 519 tothereby rotate the plate 512 and housing 504 with respect to the base524. Rotation of the housing 504 thus changes the orientation of theengaged MTU, thereby bringing that MTU into alignment with a differentstation on the processing deck.

[0239] Sensors 528, 532 are provided in opposite sides of the housing504 to indicate the position of the distributor hook 506 within thehousing 504. Sensor 528 is an end-of-travel sensor, and sensor 532 is ahome sensor. Sensors 528, 532 are preferably optical slotted sensorsavailable from Optek Technology, Inc. of Carrollton, Tex., model numberOPB980T11. For the home sensor 532, the sensor beam is broken by a homeflag 536 extending from the hook mounting structure 508 when the hook506 is in its fully retracted position. The beam of the end-of-travelsensor 528 is broken by an end-of-travel flag 534 extending from theopposite side of the hook mounting structure 508 when the hook 506 isfully extended.

[0240] An MTU-present sensor 530 mounted in the side of the housing 504senses the presence of an MTU 160 in the housing 504. Sensor 530 ispreferably a SUNX, infrared sensor, available from SUNX/Ramco Electric,Inc., of West Des Moines, Iowa.

[0241] Emperature Ramping Stations

[0242] One or more temperature ramping stations 700 are preferablydisposed below the jig plate 130 and specimen ring 250 (no temperatureramping stations located below the specimen ring 250 are shown in thefigures). After mixing the contents of the MTU 160 within the orbitalmixer 550, the right-side transport mechanism 500 may move the MTU 160from the right orbital mixer 550 to a temperature ramping station 700,depending on the assay protocol.

[0243] The purpose of each ramping station 700 is to adjust thetemperature of an MTU 160 and its contents up or down as desired. Thetemperature of the MTU and its contents may be adjusted to approximatean incubator temperature before inserting the MTU into the incubator toavoid large temperature fluctuations within the incubator.

[0244] As shown in FIGS. 17-18, a temperature ramping station 700includes a housing 702 in which an MTU 160 can be inserted. The housing702 includes mounting flanges 712, 714 for mounting the ramping station700 to the datum plate 82. A thermoelectric module 704 (also known as aPeltier device) in thermal contact with a heat sink structure 706 isattached to the housing 702, preferably at the bottom 710. Preferredthermoelectric modules are those available from Melcor, Inc. of Trenton,N.J., model number CP1.4-127-06L. Although one thermoelectric module 704is shown in FIG. 17, the ramping station 700 preferably includes twosuch thermoelectric modules. Alternatively, the outer surface of thehousing 702 could be covered with a mylar film resistive heating foilmaterial (not shown) for heating the ramping station. Suitable mylarfilm heating foils are etched foils available from Minco Products, Inc.of Minneapolis, Minn. and from Heatron, Inc. of Leavenworth, Kans. Forramp-up stations (i.e., heaters), resistive heating elements arepreferably used, and for ramp-down stations (i.e., chillers),thermoelectric modules 704 are preferably used. The housing 702 ispreferably covered with a thermal insulating jacket structure (notshown).

[0245] The heat sink structure used in conjunction with thethermoelectric module 704 preferably comprises an aluminum block withheat dissipating fins 708 extending therefrom.

[0246] Two thermal sensors (not shown) (preferably thermistors rated 10KOhm at 25° C.) are preferably provided at a location on or within thehousing 702 to monitor the temperature. YSI 44036 series thermistorsavailable from YSI, Inc. of Yellow Springs, Ohio are preferred. YSIthermistors are preferred because of their high accuracy and the ±0.1°C. interchangeability provided by YSI thermistors from one thermistor toanother. One of the thermal sensors is for primary temperature control,that is, it sends signals to the embedded controller for controllingtemperature within the ramping station, and the other thermal sensor isfor monitoring ramping station temperature as a back-up check of theprimary temperature control thermal sensor. The embedded controllermonitors the thermal sensors and controls the heating foils or thethermoelectric module of the ramping station to maintain a generallyuniform, desired temperature within the ramping station 700.

[0247] An MTU 160 can be inserted into the housing, supported on the MTUsupport flanges 718 which engage the connecting rib structure 164 of theMTU 160. A cut-out 720 is formed in a front edge of a side panel of thehousing 702. The cut-out 720 permits a distributor hook 506 of atransport mechanism 500 or 502 to engage or disengage the MTUmanipulating structure 166 of an MTU 160 inserted all the way into atemperature ramping station 700 by lateral movement with respectthereto.

[0248] Rotary Incubators

[0249] Continuing with the general description of the assay procedure,following sufficient temperature ramp-up in a ramping station 700, theright-side transport mechanism 500 retrieves the MTU from the rampingstation 700 and places the MTU 160 into the target capture and annealingincubator 600. In a preferred mode of operation of the analyzer 50, thetarget capture and annealing incubator 600 incubates the contents of theMTU 160 at about 60° C. For certain tests, it is important that theannealing incubation temperature not vary more than ±0.5° C. and thatamplification incubation (described below) temperature not vary morethan ±0.1° C. Consequently, the incubators are designed to provide aconsistent uniform temperature.

[0250] The details of the structure and operation of the two embodimentsof the rotary incubators 600, 602, 604 and 606 will now be described.Referring to FIGS. 19-23C, each of the incubators has housing with agenerally cylindrical portion 610, suitably mounted to the datum plate82, within an insulating jacket 612 and an insulated cover 611.

[0251] The cylindrical portion 610 is preferably constructed ofnickel-plated cast aluminum and the metal portion of the cover 611 ispreferably machined aluminum. The cylindrical portion 610 is preferablymounted to the datum plate 82 atop three or more resin “feet” 609. Thefeet 609 are preferably comprised of {fraction (1/2)} supplied byGeneral Electric Plastics. The material is a poor thermal conductor, andtherefore the feet 609 function to thermally isolate the incubator fromthe datum plate. The insulation 612 and the insulation for the cover 611are preferably comprised of {fraction (1/2)} inch thick polyethylenesupplied by the Boyd Corporation of Pleasantown, Calif.

[0252] Receptacle access openings 614, 616 are formed in the cylindricalportion 610, and cooperating receptacle access openings 618, 620 areformed in the jacket 612. For incubators 600 and 602, one of the accessopenings is positioned to be accessible by the right-side transportmechanism 500 and the other access opening is positioned to beaccessible by the left-side transport mechanism 502. Incubators 604 and606 need to be accessible only by the left-side transport mechanism 502and therefore only have a single receptacle access opening.

[0253] Closure mechanisms comprising revolving doors 622, 624 arerotatably positioned within the openings 614 and 616. Each revolvingdoor 622, 624 has a MTU slot 626 extending through a solid cylindricalbody. The MTU slot 626 is configured to closely match the profile of theMTU 160, having a wider upper portion compared to the lower portion. Adoor roller 628, 630 is attached on top of each of the doors 622, 624,respectively. The revolving doors 622, 624 are actuated by solenoids(not shown) which are controlled by commands from the assay managerprogram to open and close the doors 622, 624 at the proper times. A door622 or 624 is opened by turning the door 622, 624 so that the MTU slot626 thereof is aligned with the respective receptacle access opening614, 616 and is closed by turning the door 622, 624 so that the MTU slot626 thereof extends transversely to the respective access opening 614,616. The cylindrical portion 610, cover 611, doors 622, 624, and a floorpanel (not shown) constitute an enclosure which defines the incubationchamber.

[0254] The doors 622, 624 are opened to permit insertion or retrieval ofan MTU into or from an incubator and are closed at all other times tominimize heat loss from the incubator through the access openings 614,616.

[0255] A centrally positioned radial fan 632 is driven by an internalfan motor (not shown). A Papst, model number RER 100-25/14 centrifugalfan, available from ebm/Papst of Farmington, Conn., having a 24VDC motorand rated at 32 cfm is preferred because its shape is well-suited toapplication within the incubator.

[0256] Referring now to FIG. 22, an MTU carousel assembly 671 is apreferred receptacle carrier which carries a plurality of radiallyoriented, circumferentially-arranged MTUs 160 within the incubator. TheMTU carousel assembly 671 is carried by a top plate 642, which issupported by the cylindrical portion 610 of the housing, and ispreferably actuated by a rotation motor 640, preferably a stepper motor,supported at a peripheral edge of on the top plate 642. Rotation motor640 is preferably a VEXTA stepper motor, model number PKb 246l -01A,available from Oriental Motor Co., Ltd. of Tokyo, Japan.

[0257] The MTU carousel 671 includes a hub 646 disposed below the topplate 642 and coupled, via a shaft 649 extending through the top plate642, to a pulley 644. Pulley 644 is preferably a custom-made pulley withone hundred sixty-two (162) axial grooves disposed around its perimeterand is coupled to motor 640 through a belt 643, so that motor 640 canrotate the hub 646. Belt 643 is preferably a GT® series timing beltavailable from SDP/SI of New Hyde Park, N.Y. A 9:1 ratio is preferablyprovided between the pulley 644 and the motor 640. The hub 646 has aplurality of equally spaced-apart internal air flow slots 645 optionallyseparated by radially-oriented, circumferentially arranged divider walls647. In the illustration, only three divider walls 647 are shown,although it will be understood that divider walls may be provided aboutthe entire circumference of the hub 646. In the preferred embodiment,divider walls 647 are omitted. A support disk 670 is attached to hub 646and disposed below top plate 642 in generally parallel relationtherewith. A plurality of radially extending, circumferentially-arrangedMTU holding members 672 are attached to the bottom of the support disk670 (only three MTU holding members 672 are shown for clarity). The MTUholding members 672 have support ridges 674 extending along oppositesides thereof. Radially oriented MTUs are carried on the MTU carouselassembly 671 within stations 676 defined by circumferentially adjacentMTU holding members 672, with the support ridges 674 supporting theconnecting rib structures 164 of each MTU 160 carried by the MTUcarousel assembly 671.

[0258] The MTU carousel assembly rotates on a carousel drive shaft towhich the drive pulley (644 in the illustrated embodiment) is attached.A carousel position encoder is preferably mounted on an exterior end ofthe carousel drive shaft. The carousel position encoder preferablycomprises a slotted wheel and an optical slot switch combination (notshown). The slotted wheel can be coupled to the carousel assembly 671 torotate therewith, and the optical slot switch can be fixed to thecylindrical portion 610 of the housing or top plate 642 so as to bestationary. The slotted wheel/slot switch combination can be employed toindicate a rotational position of the carousel assembly 671 and canindicate a “home” position (e.g., a position in which an MTU station 676designated the #1 station is in front of the access opening 614). A2series encoders from U.S. Digital in Seattle, Wash., model numberA2-S-K-315-H, are preferred.

[0259] A heat source is provided in thermal communication with theincubator chamber defined within the incubator housing comprising thecylindrical portion 610 and cover 611. In the preferred embodiment,Mylar film-encased electrically-resistive heating foils 660 surround thehousing 610 and may be attached to the cover 611 as well. Preferredmylar film heating foils are etched foils available from Minco Products,Inc. of Minneapolis, Minn. and Heatron, Inc. of Leavenworth, Kans.Alternative heat sources may include internally mounted resistiveheating elements, thermal-electric heating chips (Peltiers), or a remoteheat-generating mechanism thermally connected to the housing by aconduit or the like.

[0260] As shown in FIGS. 19 and 22, a pipette slot 662 extends throughthe incubator cover 611, radially-aligned pipette holes 663 extendthrough the top plate 642, and pipettes slots 664 are formed in thesupport disk 670 over each MTU station 676, to allow pipetting ofreagents into MTUs disposed within the incubators. In the preferredembodiment of the analyzer 50 for the preferred mode of operation, onlytwo of the incubators, the amplification incubator 604 and thehybridization protection assay incubator 606, include the pipette holes663 and pipette slots 662 and 664, because, in the preferred mode ofoperation, it is only in these two incubators where fluids are dispensedinto MTUs 160 while they are in the incubator.

[0261] Two temperature sensors 666, preferably thermistors (10 KOhm at25° C.), are positioned in the top plate 642. YSI 44036 seriesthermistors available from YSI, Inc. of Yellow Springs, Ohio arepreferred. YSI thermistors are preferred because of their high accuracyand the ±0. 1° C. interchangeability provided by YSI thermistors fromone thermistor to another. One of the sensors 666 is for primarytemperature control, that is, it sends singles to the embeddedcontroller for controlling temperature within the incubator, and theother sensor is for monitoring temperature of the incubator as a back-upcheck of the primary temperature control sensor. The embedded controllermonitors the sensors 666 and controls the heating foils 660 and fan 632to maintain a uniform, desired temperature within the incubator housing610.

[0262] As a transport mechanism 500, 502 prepares to load an MTU 160into an incubator 600, 602, 604, or 606, the motor 640 turns the hub 646to bring an empty MTU station 676 into alignment with the receptacleaccess opening 614 (or 616). As this occurs, the door-actuating solenoidcorrespondingly turns the revolving door 622 (or 624) one-quarter turnto align the MTU slot 626 of the door with the MTU station 676. Theaccess opening 614 is thus exposed to allow placement or removal of anMTU 160. The transport mechanism 500 or 502 then advances thedistributor hook 506 from the retracted position to the extendedposition, pushing the MTU 160 out of the housing 504, through the accessopening 614, and into an MTU station 676 in the incubator. After thedistributor hook 506 is withdrawn, the motor 640 turns the hub 646,shifting the previously inserted MTU 160 away from the access opening614, and the revolving door 622 closes once again. This sequence isrepeated for subsequent MTUs inserted into the rotary incubator.Incubation of each loaded MTU continues as that MTU advances around theincubator (counter-clockwise) towards the exit slot 618.

[0263] An MTU sensor (preferably an infrared optical reflective sensor)in each of the MTU stations 676 detects the presence of an MTU 160within the station. Optek Technology, Inc. sensors, model numberOPB770T, available from Optek Technology, Inc. of Carrollton, Tex. arepreferred because of the ability of these sensors to withstand the hightemperature environment of the incubators and because of the ability ofthese sensors to read bar code data fixed to the label-receivingsurfaces 175 of the label-receiving structures 174 of the MTUs 160. Inaddition, each door assembly (revolving doors 622, 624) preferablyincludes slotted optical sensors (not shown) to indicate door open anddoor closed positions. Sensors available from Optek Technology, Inc. ofCarrollton, Tex., model number OPB980T11, are preferred because of therelatively fine resolution provided thereby to permit accuratemonitoring of door position. A skewed disk linear mixer (also known as awobbler plate) 634 is provided within housing 610 adjacent MTU carouselassembly 671 and operates as a receptacle mixing mechanism. The mixer634 comprises a disk mounted in a skewed manner to the shaft of a motor636 which extends through opening 635 into the housing 610. The motor ispreferably a VEXTA stepper motor, model number PK264-01A, available fromOriental Motors Ltd. of Tokyo, Japan, which is the same motor preferablyused for the MTU carousel assembly 671. A viscous harmonic damper 638 ispreferably attached to motor 636 to damp out harmonic frequencies of themotor which can cause the motor to stall. Preferred harmonic dampers areVEXTA harmonic dampers, available from Oriental Motors Ltd. Theoperation of the skewed disk linear mixer 634 will be described below.

[0264] Only two of the incubators, the amplification incubator 604 andthe hybridization protection assay incubator 606, include a skewed disklinear mixer 634, because, in the preferred mode of operation, it isonly in these two incubators where fluids are dispensed into the MTUs160 while they are in the incubator. Thus, it is only necessary toprovide linear mixing of the MTU 160 by the skewed disk linear mixer 634in the amplification incubator 604 and the hybridization protectionassay incubator 606.

[0265] To effect linear mixing of an MTU 160 in the incubator by linearmixer 634, the MTU carousel assembly 671 moves the MTU 160 intoalignment with the skewed disk linear mixer 634, and the skewed disk ofthe skewed disk linear mixer 634 engages the MTU manipulating structure166 of the MTU 160. As the motor 636 spins the skewed disk of the skeweddisk linear mixer 634, the portion of the skewed disk structure engagedwith the MTU 160 moves radially in and out with respect to the wall ofthe housing 610, thus alternately engaging the vertical piece 167 of theMTU manipulating structure 166 and the shield structure 169.Accordingly, the MTU 160 engaged with the skewed disk linear mixer 634is moved radially in and out, preferably at high frequency, providinglinear mixing of the contents of the MTU 160. For the amplificationincubation step of the preferred mode of operation, which occurs withinthe amplification incubator 604, a mixing frequency of 10 Hz ispreferred. For the probe incubation step of the preferred mode ofoperation, which occurs within the hybridization protection assayincubator 606, a mixing frequency of 14 Hz is preferred. Finally, forthe select incubation step of the preferred mode of operation, whichalso occurs within the hybridization protection assay incubator 606, amixing frequency of 13 Hz is preferred.

[0266] The raised arcuate portions 171, 172 may be provided in themiddle of the convex surfaces of the vertical piece 167 and the shieldstructure 169 of the MTU 160, respectively, (see FIG. 60) to minimizethe surface contact between the skewed disk linear mixer 634 and the MTU160 so as to minimize friction between the MTU 160 and the skewed disklinear mixer 634.

[0267] In the preferred embodiment, a sensor is provided at the skeweddisk linear mixer 634 to ensure that the skewed disk linear mixer 634stops rotating in the “home” position shown in FIG. 21, so that MTUmanipulating structure 166 can engage and disengage from the skewed disklinear mixer 634 as the MTU carousel assembly 671 rotates. The preferred“home” sensor is a pin extending laterally from the skewed disk linearmixer structure and a slotted optical switch which verifies orientationof the skewed disk linear mixer assembly when the pin interrupts theoptical switch beam. Hall effect sensors based on magnetism may also beused.

[0268] An alternate MTU carousel assembly and carousel drive mechanismare shown in FIGS. 23A and 23C. As shown in FIG. 23A, the alternateincubator includes a housing assembly 1650 generally comprising acylindrical portion 1610 constructed of nickel-plated cast aluminum, acover 1676 preferably formed of machined aluminum, insulation 1678 forthe cover 1676, and an insulation jacket 1651 surrounding thecylindrical portion 1610. As with the previously described incubatorembodiment, the incubator may include a linear mixer mechanism includinga linear mixer motor 636 with a harmonic damper 638. A closure mechanism1600 (described below) operates to close off or permit access through areceptacle access opening 1614. As with the previously describedembodiment, the incubator may include one or two access openings 1614depending on the location of the incubator and its function within theanalyzer 50.

[0269] A centrifugal fan 632 is mounted at a bottom portion of thehousing 1650 and is driven by a motor (not shown). A fan cover 1652 isdisposed over the fan and includes sufficient openings to permit airflow generated by the fan 632. A carousel support shaft 1654 includes alower shaft 1692 and an upper shaft 1690 divided by a support disk 1694.The support shaft 1654 is supported by means of the lower shaft 1692extending down into the fan cover 1652 where it is rotatably supportedand secured by bearings (not shown).

[0270] An MTU carousel 1656 includes an upper disk 1658 having a centralportion 1696. A top surface of the support disk 1694 engages and isattached to a bottom surface of the central portion 1696 of the upperdisk 1658 so that the weight of the carousel 1656 is supported frombelow. As shown in FIG. 23C, a plurality of radially extending,circumferentially spaced station dividers 1660 are attached beneath theupper disk 1658. A lower disk 1662 includes a plurality of radialflanges 1682 emanating from an annular inner portion 1688. The radialflanges 1682 correspond in number and spacing to the carousel stationdividers 1660, and the lower disk 1662 is secured to the bottom surfacesof the carousel station dividers 1660, with each flange 1682 beingsecured to an associated one of the dividers 1660.

[0271] The radial flanges 1682 define a plurality of radial slots 1680between adjacent pairs of flanges 1682. As can be appreciated from FIG.23C, the width in the circumferential direction of each flange 1682 atan inner end 1686 thereof is less than the width in the circumferentialdirection of the flange 1682 at the outer end 1684 thereof. The taperedshape of the flanges 1682 ensures that the opposite sides of the slots1680 are generally parallel to one another.

[0272] When the lower disk 1662 is attached beneath the carousel stationdividers 1660, the widths of the flanges along at least a portion oftheir respective lengths are greater than the widths of the respectivedividers 1660, which may also be tapered from an outer end thereoftoward an inner end thereof. The flanges 1684 define lateral shelvesalong the sides of adjacent pairs of dividers 1660 for supporting theconnecting rib structure 164 of an MTU 160 inserted into each MTUstation 1663 defined between adjacent pairs of dividers 1660.

[0273] A pulley 1664 is secured to the top of the central portion 1696of the upper disk 1658 and a motor 1672 is carried by a mounting bracket1670 which spans the diameter of the housing 1650 and is secured to thecylindrical portion 1610 of the housing at opposite ends thereof Themotor is preferably a Vexta PK264-01A stepper motor, and it is coupledto the pulley (having a 9:1 ratio with respect to the motor) by a belt1666, preferably one supplied by the Gates Rubber Company. A positionencoder 1674 is secured to a top central portion of the mounting bracket1672 and is coupled with the upper shaft 1690 of the carousel supportshaft 1654. The encoder 1674 (preferably an absolute encoder of the A2series by U.S. Digital Corporation of Vancouver, Wash.) indicates therotational position of the carousel 1656.

[0274] An incubator cover is defined by an incubator plate 1676,preferably formed of machined aluminum, and a conforming coverinsulation element 1678. Cover plate 1676 and insulation element 1678include appropriate openings to accommodate the encoder 1674 and themotor 1672 and may also include radial slots formed therein fordispensing fluids into MTUs carried within the incubator as describedwith regard to the above embodiment.

[0275] An alternate, and preferred, closure mechanism 1600 is shown inFIG. 23B. The cylindrical portion 1610 of the incubator housing includesat least one receptacle access opening 1614 with outwardly projectingwall portions 1616, 1618 extending integrally from the cylindricalportion 1610 along opposite sides of the access opening 1614.

[0276] A rotating door 1620 is operatively mounted with respect to theaccess opening 1614 by means of a door mounting bracket 1636 attached tothe cylindrical portion 1610 of the housing above the access opening1614. Door 1620 includes an arcuate closure panel 1622 and atransversely extending hinge plate portion 1628 having a hole 1634 forreceiving a mounting post (not shown) of the door mounting bracket 1636.The door 1622 is rotatable about the opening 1634 with respect to theaccess opening 1614 between a first position in which the arcuateclosure panel 1622 cooperates with the projecting wall portions 1616,161100to close off the access opening 1614 and a second position rotatedoutwardly with respect to the access opening 1614 to permit movement ofa receptacle through the access opening 1614. An inner arcuate surfaceof the arcuate panel 1622 conforms with an arcuate surface 1638 of thedoor mounting bracket 1636 and an arcuate surface 1619 disposed belowthe receptacle access opening 1614 to permit movement of the arcuatepanel 1622 with respect to the surfaces 1638 and 1619 while providing aminimum gap between the respective surfaces so as to minimize heat losstherethrough.

[0277] The door 1620 is actuated by a motor 1642 mounted to theincubator housing by means of a motor mounting bracket 1640 secured tothe cylindrical portion 1610 of the housing beneath the receptacleaccess opening 1614. A motor shaft 1644 is coupled to a lower actuatingplate 1626 of the rotating door 1620 so that rotation of the shaft 1644is transmitted into rotation of the rotating door 1620. Motor 1642 ismost preferably an HSI 7.5° per step motor available from Haydon Switchand Instrument, Inc. of Waterbury, Conn. The HSI motor is chosen becauseof its relatively low cost and because the closure assembly 1600 doesnot require a high torque, robust motor.

[0278] Door position sensors 1646 and 1648 (preferably slotted opticalsensors) are operatively mounted on opposite sides of the door mountingbracket 1636. The sensor 1646 and 1648 cooperate with sensor tabs 1632and 1630 on the hinge plate 1628 of the door 1620 for indicating therelative position of the rotating door 1620 and can be configured so asto indicate, for example, a door open and a door closed status.

[0279] A door cover element 1612 is secured to the outside of thecylindrical portion 1610 of the housing so as to cover the door mountingbracket 1636 and a portion of the rotating door 1620. The cover element1612 includes an access opening 1613 aligned with the access opening1614 of the incubator housing and further includes a receptacle bridge1615 extending laterally from a bottom edge of the access opening 1613.The receptacle bridge 1615 facilitates the insertion of a receptacle(e.g., an MTU 160) into and withdrawal of the receptacle from theincubator.

[0280] While in the target capture and annealing incubator 600, the MTU160 and test specimens are preferably kept at a temperature of about 60°C.±0.5° C. for a period of time sufficient to permit hybridizationbetween capture probes and target nucleic acids. Under these conditions,the capture probes will preferably not hybridize with thosepolynucleotides directly immobilized by the magnetic particles.

[0281] Following target capture incubation in the target capture andannealing incubator 600, the MTU 160 is rotated by the incubatorcarousel to the entrance door 622, also known as the right-side ornumber one distributor door. The MTU 160 is retrieved from its MTUstation 676 within incubator 600 and is then transferred by theright-side transport mechanism 500 to a temperature ramp-down station(not shown) below the specimen ring 250. In the ramp-down station, theMTU temperature is brought down to the level of the next incubator. Thisramp-down station that precedes the active temperature and pre-readcool-down incubator 602 is technically a heater, as opposed to achiller, because the temperature to which the MTU is decreased, about40° C., is still greater than the ambient analyzer temperature, about30° C. Accordingly, this ramp-down station preferably uses resistiveheating elements, as opposed to a thermoelectric module.

[0282] From the ramp-down station, the MTU 160 is transferred by theright-side transfer mechanism 500 into the active temperature andpre-read cool-down incubator 602. The design and operation of the activetemperature and pre-read cool-down 602 is similar to that of the targetcapture and annealing incubator 600, as described above, except that theactive temperature and pre-read cool-down incubator 602 incubates at40±1.0° C.

[0283] In the AT incubator 602, the hybridization conditions are suchthat the polythymidine tail of the immobilized polynucleotide canhybridize to the polyadenine tail of the capture probe. Provided targetnucleic acid has hybridized with the capture probe in the annealingincubator 600, a hybridization complex can be formed between theimmobilized polynucleotide, the capture probe and the target nucleicacid in the AT incubator 602, thus immobilizing the target nucleic acid.In the AT incubator 602, the hybridization conditions are such that thepolythymidine tail of the immobilized polynucleotide can hybridize tothe polyadenine tail of the capture probe. Provided target nucleic acidhas hybridized with the capture probe in the annealing incubator 600, ahybridization complex can be formed between the immobilizedpolynucleotide, the capture probe and the target nucleic acid in the ATincubator 602, thus immobilizing the target nucleic acid.

[0284] During active temperature binding incubation, the carouselassembly 1656 (or 671) of the active temperature and pre-read cool-downincubator 602 rotates the MTU to the exit door 624, also known as thenumber two, or left-side, distributor door, from which the MTU 160 canbe removed by the left-side transport mechanism 502. The left-sidetransport mechanism 502 removes the MTU 160 from the active temperatureand pre-read cool-down incubator 602 and places it into an availablemagnetic separation wash station 800.

[0285] Temperature ramping stations 700 can be a bottle neck in theprocessing of a number of MTUs through the chemistry deck 200. It may bepossible to use underutilized MTU stations 676 in one or more of theincubators in which temperature sensitivity is of less concern. Forexample, the active temperature binding process which occurs within theactive temperature and pre-read cool-down incubator 602 at about 40° C.is not as temperature sensitive as the other incubators, and up tofifteen (15) of the incubator's thirty (30) MTU stations 676 may beunused at any given time. As presently contemplated, the chemistry deckhas only about eight ramp-up stations, or heaters. Accordingly,significantly more MTUs can be preheated within the unused slots of theactive temperature and pre-read cool-down incubator 602 than within theramp-up stations 700. Moreover, using unused incubator slots instead ofheaters allows the omission of some or all of the heaters, thus freeingup space on the chemistry deck.

[0286] Magnetic Separation Wash Stations

[0287] Turning to FIGS. 24-25, each magnetic separation wash station 800includes a module housing 802 having an upper section 801 and a lowersection 803. Mounting flanges 805, 806 extend from the lower section 803for mounting the magnetic separation wash station 800 to the datum plate82 by means of suitable mechanical fasteners. Locator pins 807 and 811extend from the bottom of lower section 803 of housing 802. Pins 807 and811 register with apertures (not shown) formed in the datum plate 82 tohelp to locate the magnetic separation wash station 800 on the datumplate 82 before the housing 802 is secured by fasteners.

[0288] A loading slot 804 extends through the front wall of the lowersection 803 to allow a transport mechanism (e.g. 502) to place an MTU160 into and remove an MTU 160 from the magnetic separation station 800.A tapered slot extension 821 surrounds a portion of the loading slot 804to facilitate MTU insertion through the slot 804. A divider 808separates the upper section 801 from the lower section 803.

[0289] A pivoting magnet moving structure 810 is attached inside thelower section 803 so as to be pivotable about point 812. The magnetmoving structure 810 carries permanent magnets 814, which are positionedon either side of an MTU slot 815 formed in the magnet moving structure810. Preferably five magnets, one corresponding to each individualreceptacle vessel 162 of the MTU 160, are held in an aligned arrangementon each side of the magnet moving structure 810. The magnets arepreferably made of neodymium-iron-boron (NdFeB), minimum grade n-35 andhave preferred dimensions of 0.5 inch width, 0.3 inch height, and 0.3inch depth. An electric actuator, generally represented at 816, pivotsthe magnet moving structure 810 up and down, thereby moving the magnets814. As shown in FIG. 25, actuator 816 preferably comprises a rotarystepper motor 819 which rotates a drive screw mechanism coupled to themagnet moving structure 810 to selectively raise and lower the magnetmoving structure 810. Motor 819 is preferably an HSI linear stepperactuator, model number 26841-05, available from Haydon Switch andInstrument, Inc. of Waterbury, Conn.

[0290] A sensor 818, preferably an optical slotted sensor, is positionedinside the lower section 803 of the housing for indicating the down, or“home”, position of the magnet moving structure 810. Sensor 818 ispreferably an Optek Technology, Inc., model number OPB980T11, availablefrom Optek Technology, Inc. of Carrollton, Tex. Another sensor 817, alsopreferably an Optek Technology, Inc., model number OPB980T11, opticalslotted sensor, is preferably provided to indicate the up, or engaged,position of the magnet moving structure 810.

[0291] An MTU carrier unit 820 is disposed adjacent the loading slot804, below the divider 808, for operatively supporting an MTU 160disposed within the magnetic separation wash station 800. Turning toFIG. 26, the MTU carrier unit 820 has a slot 822 for receiving the upperend of an MTU 160. A lower fork plate 824 attaches to the bottom of thecarrier unit 820 and supports the underside of the connecting ribstructure 164 of the MTU 160 when slid into the carrier unit 820 (seeFIGS. 27 and 28). A spring clip 826 is attached to the carrier unit 820with its opposed prongs 831, 833 extending into the slot 822 toreleasably hold the MTU within the carrier unit 820.

[0292] An orbital mixer assembly 828 is coupled to the carrier unit 820for orbitally mixing the contents of an MTU held by the MTU carrier unit820. The orbital mixer assembly 828 includes a stepper motor 830 mountedon a motor mounting plate 832, a drive pulley 834 having an eccentricpin 836, an idler pulley 838 having an eccentric pin 840, and a belt 835connecting drive pulley 834 with idler pulley 838. Stepper motor 830 ispreferably a VEXTA, model number PK245-02A, available from OrientalMotors Ltd. of Tokyo, Japan, and belt 835 is preferably a timing belt,model number A 6G16-170012, available from SDP/SI of New Hyde Park, N.Y.As shown in FIGS. 25 and 26, eccentric pin 836 fits within a slot 842formed longitudinally in the MTU carrier unit 820. Eccentric pin 840fits within a circular aperture 844 formed in the opposite end of MTUcarrier unit 820. As the motor 830 turns the drive pulley 834, idlerpulley 838 also rotates via belt 835 and the MTU carrier unit 820 ismoved in a horizontal orbital path by the eccentric pins 836, 840engaged with the apertures 842, 844, respectively, formed in the carrierunit 820. The rotation shaft 839 of the idler pulley 838 preferablyextends upwardly and has a transverse slot 841 formed therethrough. Anoptical slotted sensor 843 is disposed at the same level as the slot 841and measures the frequency of the idler pulley 838 via the sensor beamintermittently directed through slot 841 as the shaft 839 rotates.Sensor 843 is preferably an Optek Technology, Inc., model numberOPB980T11, sensor, available from Optek Technology, Inc. of Carrollton,Tex.

[0293] Drive pulley 834 also includes a locator plate 846. Locator plate846 passes through slotted optical sensors 847, 848 mounted to a sensormounting bracket 845 extending from motor mounting plate 832. Sensors847, 848 are preferably Optek Technology, Inc., model number OPB980T11,sensors, available from Optek Technology, Inc. of Carrollton, Tex.Locator plate 846 has a plurality of circumferentially spaced axialopenings formed therein which register with one or both sensors 847, 848to indicate a position of the orbital mixer assembly 828, and thus aposition of the MTU carrier unit 820.

[0294] Returning to FIG. 24, wash buffer solution delivery tubes 854connect to fittings 856 and extend through a top surface of the modulehousing 802. Wash buffer delivery tubes 854 extend through the divider808 via fittings 856, to form a wash buffer delivery network.

[0295] As shown in FIGS. 27 and 28, wash buffer dispenser nozzles 858extending from the fittings 856 are disposed within the divider 808.Each nozzle is located above a respective receptacle vessel 162 of theMTU 160 at a laterally off-center position with respect to thereceptacle vessel 162. Each nozzle includes a laterally-directed lowerportion 859 for directing the wash buffer into the respective receptaclevessel from the off-center position. Dispensing fluids into thereceptacle vessels 162 in a direction having a lateral component canlimit splashing as the fluid runs down the sides of the respectivereceptacle vessels 162. In addition, the laterally directed fluid canrinse away materials clinging to the sides of the respective receptaclevessels 162.

[0296] As shown in FIGS. 24 and 25, aspirator tubes 860 extend through atube holder 862, to which the tubes 860 are fixedly secured, and extendthrough openings 861 in the divider 808. A tube guide yoke 809 (see FIG.26) is attached by mechanical fasteners to the side of divider 808,below openings 861. Aspirator hoses 864 connected to the aspirator tubes860 extend to the vacuum pump 1162 (see FIG. 52) within the analyzer 50,with aspirated fluid drawn off into a fluid waste container carried inthe lower chassis 1100. Each of the aspirator tubes 860 has a preferredlength of 12 inches with an inside diameter of 0.041 inches.

[0297] The tube holder 862 is attached to a drive screw 866 actuated bya lift motor 868. Lift motor 868 is preferably a VEXTA, model numberPK245-02A, available from Oriental Motors Ltd. of Tokyo, Japan, and thedrive screw 866 is preferably a ZBX series threaded anti-backlash leadscrew, available from Kerk Motion Products, Inc. of Hollis, N.H. Thetube holder 862 is attached to a threaded sleeve 863 of the drive screw866. Rod 865 and slide rail 867 function as a guide for the tube holder862. Z-axis sensors 829, 827 (slotted optical sensors) cooperate with atab extending from threaded sleeve 863 to indicate top and bottom ofstroke positions of the aspirator tubes 860. The Z-axis sensors arepreferably Optek Technology, Inc., model number OPB980T11, sensors,available from Optek Technology, Inc. of Carrollton, Tex.

[0298] Cables bring power and control signals to the magnetic separationwash station 800, via a connector 870.

[0299] The magnet moving structure 810 is initially in a down position(shown in phantom in FIG. 25), as verified by the sensor 818, when theMTU 160 is inserted into the magnetic separation wash station 800through the insert opening 804 and into the MTU carrier unit 820. Whenthe magnet moving structure 810 is in the down position, the magneticfields of the magnets 814 will have no substantial effect on themagnetically responsive particles contained in the MTU 160. In thepresent context, “no substantial effect” means that the magneticallyresponsive particles are not drawn out of suspension by the attractionof the magnetic fields of the magnets 814. The orbital mixer assembly828 moves the MTU carrier unit 820 a portion of a complete orbit so asto move the carrier unit 820 and MTU 160 laterally, so that each of thetiplets 170 carried by the tiplet holding structures 176 of the MTU 160is aligned with each of the aspiration tubes 860, as shown in FIG. 28.The position of the MTU carrier unit 820 can be verified by the locatorplate 846 and one of the sensors 847, 848. Alternatively, the steppermotor 830 can be moved a known number of steps to place the MTU carrierunit 820 in the desired position, and one of the sensors 847, 848 can beomitted.

[0300] The tube holder 862 and aspirator tubes 860 are lowered by thelift motor 868 and drive screw 866 until each of the aspirator tubes 860frictionally engages a tiplet 170 held in an associated carryingstructure 176 on the MTU 160.

[0301] As shown in FIG. 25A, the lower end of each aspirator tube 860 ischaracterized by a tapering, step construction, whereby the tube 860 hasa first portion 851 along most of the extent of the tube, a secondportion 853 having a diameter smaller than that of the first portion851, and a third portion 855 having a diameter smaller than that of thesecond portion 853. The diameter of the third portion 855 is such as topermit the end of the tube 860 to be inserted into the flared portion181 of the through hole 180 of the tiplet 170 and to create aninterference friction fit between the outer surface of third portion 855and the two annular ridges 183 (see FIG. 59) that line the inner wall ofhole 180 of tiplet 170. An annular shoulder 857 is defined at thetransition between second portion 853 and third portion 855. Theshoulder 857 limits the extent to which the tube 860 can be insertedinto the tiplet 170, so that the tiplet can be stripped off after use,as will be described below.

[0302] The tiplets 170 are at least partially electrically conductive,so that the presence of a tiplet 170 on an aspirator tube 860 can beverified by the capacitance of a capacitor comprising the aspiratortubes 860 as one half of the capacitor and the surrounding hardware ofthe magnetic separation wash station 800 as the other half of thecapacitor. The capacitance will change when the tiplets 170 are engagedwith the ends of the aspirator tubes 860.

[0303] In addition, five optical slotted sensors (not shown) can bestrategically positioned above the divider 808 to verify the presence ofa tiplet 170 on the end of each aspirator tube 860. Preferred“tiplet-present” sensors are Optek Technology, Inc., model numberOPB930W51, sensors, available from Optek Technology, Inc. of Carrollton,Tex. A tiplet 170 on the end of an aspirator tube 860 will break thebeam of an associated sensor to verify presence of the tiplet 170. If,following a tiplet pick-up move, tiplet engagement is not verified bythe tiplet present sensors for all five aspirator tubes 860, the MTU 160must be aborted. The aborted MTU is retrieved from the magneticseparation wash station 800 and sent to the deactivation queue 750 andultimately discarded.

[0304] After successful tiplet engagement, the orbital mixer assembly828 moves the MTU carrier unit 820 back to a fluid transfer positionshown in FIG. 27 as verified by the locator plate 846 and one or both ofthe sensors 847, 848.

[0305] The magnet moving structure 810 is then raised to the up positionshown in FIG. 24 so that the magnets 814 are disposed adjacent oppositesides of the MTU 160. With the contents of the MTU subjected to themagnetic fields of the magnets 814, the magnetically responsiveparticles bound indirectly to the target nucleic acids will be drawn tothe sides of the individual receptacle vessels 162 adjacent the magnets814. The remaining material within the receptacle vessels 162 should besubstantially unaffected, thereby isolating the target nucleic acids.The magnet moving structure 810 will remain in the raised position foran appropriate dwell time, as defined by the assay protocol andcontrolled by the assay manager program, to cause the magnetic particlesto adhere to the sides of the respective receptacle vessels 162.

[0306] The aspirator tubes are then lowered into the receptacle vessels162 of the MTU 160 to aspirate the fluid contents of the individualreceptacle vessels 162, while the magnetic particles remain in thereceptacle vessels 162, adhering to the sides thereof, adjacent themagnets 814. The tiplets 170 at the ends of the aspirator tubes 860ensure that the contents of each receptacle vessel 162 do not come intocontact with the sides of the aspirator tubes 860 during the aspiratingprocedure. Because the tiplets 170 will be discarded before a subsequentMTU is processed in the magnetic separation wash station 800, the chanceof cross-contamination by the aspirator tubes 860 is minimized.

[0307] The electrically conductive tiplets 170 can be used in a knownmanner for capacitive fluid level sensing within the receptacle vessels162 of the MTUs. The aspirator tubes 860 and the conductive tiplets 170comprise one half of a capacitor, the surrounding conductive structurewithin the magnetic separation wash station comprises the second half ofthe capacitor, and the fluid medium between the two halves of thecapacitor constitutes the dielectric. Capacitance changes due to achange in the nature of the dielectric can be detected.

[0308] The capacitive circuitry of the aspirator tubes 860 can bearranged so that all five aspirator tubes 860 operate as a single ganglevel-sensing mechanism. As a gang level-sensing mechanism, thecircuitry will only determine if the fluid level in any of thereceptacle vessels 162 is high, but cannot determine if the fluid levelin one of the receptacle vessels is low. In other words, when any of theaspirator tubes 860 and its associated tiplet 170 contacts fluidmaterial within a receptacle vessel, capacitance of the system changesdue to the change in the dielectric. If the Z-position of the aspiratortubes 860 at which the capacitance change occurs is too high, then ahigh fluid level in at least one receptacle vessel is indicated, thusimplying an aspiration failure. On the other hand, if the Z-position ofthe aspirator tubes at which the capacitance change occurs is correct,the circuitry cannot differentiate between aspirator tubes, and,therefore, if one or more of the other tubes has not yet contacted thetop of the fluid, due to a low fluid level, the low fluid level will goundetected.

[0309] Alternatively, the aspirator tube capacitive circuitry can bearranged so that each of the five aspirator tubes 860 operates as anindividual level sensing mechanism.

[0310] With five individual level sensing mechanisms, the capacitivelevel sensing circuitry can detect failed fluid aspiration in one ormore of the receptacle vessels 162 if the fluid level in one or more ofthe receptacle vessels is high. Individual capacitive level sensingcircuitry can detect failed fluid dispensing into one or more of thereceptacle vessels 162 if the fluid level in one or more of thereceptacle vessels is low. Furthermore, the capacitive level sensingcircuitry can be used for volume verification to determine if the volumein each receptacle vessel 162 is within a prescribed range. Volumeverification can be performed by stopping the descent of the aspiratortubes 860 at a above expected fluid levels, e.g. 110% of expected fluidlevels, to make sure the receptacle vessels has a level that high, andthen stopping the descent of the aspirator tubes 860 at a position belowthe expected fluid levels, e.g. 90% of expected fluids levels, to makesure that each of the receptacle vessels has a fluid level at least that

[0311] Following aspiration, the aspirator tubes 860 are raised, themagnet moving structure 810 is lowered, and a prescribed volume of washbuffer is dispensed into each receptacle vessel 162 of the MTU 160through the wash buffer dispenser nozzles 858. To prevent hanging dropsof wash buffer on the wash buffer dispenser nozzles 858, a brief,post-dispensing air aspiration is preferred.

[0312] The orbital mixer assembly 828 then moves the MTU carriers 820 ina horizontal orbital path at high frequency to mix the contents of theMTU 160. Mixing by moving, or agitating, the MTU in a horizontal planeis preferred so as to avoid splashing the fluid contents of the MTU andto avoid the creation of aerosols. Following mixing, the orbital mixerassembly 828 stops the MTU carrier unit 820 at the fluid transfer

[0313] To further purify the targeted nucleic acids, the magnet movingstructure 810 is a again raised and maintained in the raised positionfor a prescribed dwell period. After magnetic dwell, the aspirator tubes860 with the engaged tiplets 170 are lowered to the bottoms of thereceptacle vessels 162 of the MTU 160 to aspirate the test specimenfluid and wash buffer in an aspiration procedure essentially the same asthat described above.

[0314] One or more additional wash cycles, each comprising a dispense,mix, magnetic dwell, and aspirate sequence, may be performed as definedby the assay protocol. Those skilled in the art of nucleic acid-baseddiagnostic testing will be able to determine the appropriate magneticdwell times, number of wash cycles, wash buffers, etc. for a desiredtarget capture procedure.

[0315] While the number of magnetic separation wash stations 800 canvary, depending on the desired throughput, analyzer 50 preferablyincludes five magnetic separation wash stations 800, so that a magneticseparation wash procedure can be performed on five different MTUs inparallel.

[0316] After the final wash step, the magnet moving structure 810 ismoved to the down position and the MTU 160 is removed from the magneticseparation wash station 800 by the left-side transport mechanism 502 andis then placed into the left orbital mixer 552.

[0317] After the MTU 160 is removed from the wash station, the tiplets170 are stripped from the aspiration tubes 860 by a stripper plate 872located at the bottom of the lower section 803 of the housing 802.

[0318] The stripper plate 872 has a number of aligned stripping holes871 corresponding in number to the number of aspiration tubes 860, whichis five in the preferred embodiment. As shown in FIGS. 29A to 29D, eachstripping hole 871 includes a first portion 873, a second portion 875smaller than first portion 873, and a bevel 877 surrounding portions 873and 875. The stripper plate 872 is oriented in the bottom of the housing802 so that the small portion 875 of each stripping hole 871 isgenerally aligned with each associated aspiration tube 860, as shown inFIG. 29A. The aspiration tubes 860 are lowered so that the tiplet 170 atthe end of each aspirator tube 860 engages the stripping hole 871. Smallportion 875 is too small to accommodate the diameter of a tiplet 170, sothe bevel 877 directs the tiplet 170 and the aspirator tube 860 towardthe larger portion 873, as shown in FIG. 29B. The aspirator tubes 860are made of an elastically flexible material, preferably stainlesssteel, so that, as the aspirator tubes 860 continue to descend, thebeveled portion 877 causes each of aspirator tubes 860 to deflectlaterally. The small portion 875 of the stripping hole 871 canaccommodate the diameter of the aspirator tube 860, so that after therim 177 of the tiplet 170 clears the bottom of stripping hole 871, eachof the aspirator tubes 860 snaps, due to its own resilience, into thesmall portion 875 of the stripping hole 871 as shown in FIG. 29C. Theaspirator tubes 860 are then raised, and the rim 177 of each tiplet 170engages the bottom peripheral edge of the small portion 875 of strippinghole 871. As the aspirator tubes 860 ascend further, the tiplets 170 arepulled off the aspirator tubes 860 by the stripping holes 871 (see FIG.29D). The stripped tiplets 170 are directed by a chute into a solidwaste container, such as the tiplet waste bin 1134.

[0319] The capacitance of the aspiration tubes 860 is sampled to verifythat all tiplets 170 have been stripped and discarded. The strippingstep can be repeated if necessary.

[0320] An alternate stripper plate 882 is shown in FIGS. 31A to 31C.Stripper plate 882 includes a number of stripping holes 881corresponding to the number of aspirator tubes 860, which is five in thepreferred embodiment. Each stripping hole 881 includes a through-hole883 surrounded by a bevelled countersink 887. A pair of tangs 885 extendlaterally from diametrically opposed positions below the through-hole883. Tangs 885 are preferably made from a spring steel and include av-notch 886 at their ends.

[0321] As an aspirator tube 860 with a tiplet 170 disposed on its end islowered toward stripping hole 881, bevelled portion 887 ensures that anymisaligned tubes are directed into the through-hole 883. The spacingbetween the ends of the opposed tangs 885 is less than the diameter ofthe tiplet 170, so as the aspirator tube 860 and tiplet 170 are lowered,the tiplet engages the tangs 885, causing them to deflect downwardly asthe tiplet 170 is forced between tangs 885. When the aspirator tubes 860are raised, the notches 886 of the tangs 885 grip the relatively softmaterial of the tiplet 170, thus preventing upward relative movement ofthe tiplet 170 with respect to the tangs 885. As the tubes continue toascend, the tangs 885 pull the tiplet 170 off the tube 860. When theaspirator tubes 860 are subsequently lowered to strip a subsequent setof tiplets, the tiplet held between the tangs from the previousstripping is pushed through the tangs by the next tiplet and is directedtoward waste bin 1134 (see FIG. 52) located in the lower chassis 1100generally below the five magnetic separation wash stations 800.

[0322] Still another alternate, and the presently preferred, stripperplate 1400 is shown in FIGS. 30A-30D. Stripper plate 1400 includes fivestripper cavities 1402, each including an initial frusto-conical portion1404. The frusto-conical portion 1404 tapers down to a neck portion 1406which connects to an enlarged straight section 1408. Straight section1408 is offset with respect to the center of neck portion 1406, so thatone side of the straight section 1408 is flush with a side of the neckportion 1406, and an opposite side of the straight section 1408 isoffset from and undercuts the side of the neck portion 1406, therebyforming a ledge 1414. Following the straight section 1408, a slopedportion 1410 is provided on a side of the stripper cavity 1402 oppositethe ledge 1414. Sloped portion 1410 tapers inwardly toward a bottomopening 1412.

[0323] As an aspirator tube 860 with a tiplet 170 on its end is movedtoward the stripper cavity 1402, the frusto-conical portion 1404 directsthe tiplet 170 and tube 860 toward the neck portion 1406. The aspiratortube 860 continues to descend, and the tiplet 170 enters the straightsection 1408 as the rim 177 of the tiplet 170 clears the bottom of thefrusto-conical portion 1404 and passes through the neck portion 1406.

[0324] If the aspirator tube 860 and the stripper cavity 1402 are inproper, preferred alignment, a portion of the rim 177 of the tiplet 170will be disposed below the ledge 1414 of the stripper cavity 1402 whenthe tiplet 170 has moved through the neck portion 1406 and into thestraight section 1408. To ensure that a portion of the rim 177 will bedisposed beneath the ledge 1414, the tiplet 170 engages the lower slopedportion 1410 as the aspirator tube 860 descends further to urge theaspirator tube laterally to direct the tiplet 170 below the ledge 1414.

[0325] The annular shoulder 857 (see FIG. 25A) formed at the bottom ofthe aspirator tube 860 ensures that the tube 860 is not forced furtherinto the through hole 180 of the tiplet 170 as the tube 860 is loweredinto the stripper cavity 1402. The aspirator tube 860 then ascends, andthe ledge 1414 catches the rim 177 and strips the tiplet 170 off thetube 860. The stripped tiplet 170 falls through bottom opening 1412 andinto the waist bin 1134 in the lower chassis 1100 (see FIG. 52).

[0326] With each of the stripper plates described above, the position ofthe tiplet-stripping elements are not all the same. For example, theledges 1414 of the stripper cavities 1402 of the stripper plate 1400 arenot at the same height throughout all the cavities. Preferably, threetiplet-stripping elements are at one height, and two tiplet-strippingelements are at a slightly different height above or below the otherthree elements. The result of the offset tiplet-stripping elements isthat the static friction of the tiplet 170 on the end of the aspiratortube 860 need not be overcome, or broken, for all five tubes 860 atonce. As the aspirator tubes 860 begin to ascend, static friction of thetiplets 170 is broken for one set (two or three) of aspirator tubes 860first, and then, as the tubes 860 continue to ascend, static friction ofthe tiplets 170 is broken for the remaining tubes 860. By not breakingstatic friction of the tiplets 170 for all five aspirator tubes 860 atonce, the loads to which the tube holder 862, drive screw 866, threadedsleeve 863, and lift motor 868 are subjected are kept to a lower level.

[0327] Orbiral Mixers

[0328] The left orbital mixer 552 (and the right orbital mixer 550), asshown in FIGS. 32-34, are constructed and operate in the same manner asthe lower housing section 803 and the orbital mixer assembly 828 of themagnetic separation wash stations 800 described above. Specifically, theorbital mixer 550 (552) includes a housing 554, including a front plate551, a back plate 559, and mounting flanges 555, 556, for mounting theorbital mixer 550 (552) to the datum plate 82. An insert opening 557 isformed in a front edge of the housing 554. An MTU carrier 558 has a forkplate 560 attached to the bottom thereof and an MTU-retaining clip 562attached to a back portion of the carrier 558 with opposed prongs of theclip 562 extending into an inner cavity of the carrier 558 thataccommodates the MTU. An orbital mixer assembly 564 includes a drivemotor 566 mounted to a motor mounting plate 567, a drive wheel 568having an eccentric pin 570, an idler wheel 572 having an eccentric pin573, and a belt 574. Drive motor 566 is preferably a stepper motor, andmost preferably a VEXTA, model number PK245-02A, available from OrientalMotors Ltd. of Tokyo, Japan. Belt 574 is preferably a timing belt, modelnumber A 6G16-170012, available from SDP/SI of New Hyde Park, N.Y. Theorbital mixer assembly 564 is coupled to the MTU carrier 558 through theeccentric pins 570, 573 to move the MTU carrier 558 in an orbital pathto agitate the contents of the MTU. The drive wheel 568 includes alocator plate 576, which, in conjunction with sensor 578 attached tosensor mounting bracket 579, verifies the proper positioning of the MTUcarrier 558 for inserting an MTU 160 into the orbital mixer 552 (550)and retrieving an MTU 160 from the orbital mixer. Sensor 578 ispreferably an Optek Technology, Inc., model number OPB980T11, sensor,available from Optek Technology, Inc. of Carrollton, Tex.

[0329] A top plate 580 is attached atop housing 554. Top plate 580 ofthe left orbital mixer 552 includes a number of tube fittings 582,preferably five, to which are coupled a like number of flexible deliverytubes (not shown) for delivering a fluid from a bulk fluid container toan MTU 160 located within the mixer via dispenser nozzles 583. Top plate580 also includes a plurality of pipette openings 581, corresponding innumber to the number of individual receptacle vessels 162 comprising asingle MTU 160, which is preferably five.

[0330] With the MTU 160 held stationary in the left orbital mixer 552,pipette unit 480 of the left pipette assembly 470 transfers a prescribedvolume of amplification reagent from a container within the reagentcooling bay 900 into each receptacle vessel 162 of the MTU 160 throughthe pipette openings 581. The amplification reagent used will dependupon the amplification procedure being followed. Various amplificationprocedures are well known to those skilled in the art of nucleicacid-based diagnostic testing, a number of which are discussed in thebackground section above.

[0331] Next, the contents of the MTU are mixed by the orbital mixerassembly 564 of the orbital mixer 552 to ensure proper exposure of thetarget nucleic acid to amplification reagent. For a desiredamplification procedure, those skilled in the art of nucleic acid-baseddiagnostic testing will be able to determine the appropriate componentsand amounts of an amplification reagent, as well as mix frequencies anddurations.

[0332] After pipetting amplification reagent into the MTU 160, thepipette unit 480 is moved to a rinse basin (described below) on theprocessing deck 200, and pipette unit 480 is washed by running distilledwater through probe 481. The distilled water is pumped from bottle 1140in the lower chassis 1100, and the purge water is collected in a liquidwaste container 1128 in the lower chassis 1100.

[0333] After mixing the contents of the MTU 160, a layer of silicon oilis dispensed into each receptacle vessel through the dispenser nozzles583. The layer of oil, pumped from bottles 1168 in the lower chassis1100, helps prevent evaporation and splashing of the fluid contents ofthe MTU 160 during subsequent manipulation and incubation of the MTU 160and its contents.

[0334] Reagent Cooling Bay

[0335] The reagent cooling bay 900 will now be described.

[0336] Referring to FIGS. 35-39, the reagent cooling bay 900 includes aninsulating jacket 902 fitted around a cylindrical housing 904,preferably made from aluminum. A cover 906, preferably made of Delrin,sits atop housing 904 with a registration tab 905 of cover 906 fittingwithin slot 907 in housing 904 to ensure proper orientation of the cover906 An optical sensor may be provided proximate to or within slot 907for verifying that tab 905 is seated within slot 907. Alternatively, anoptical sensor assembly 909 can be secured to an edge of an upper rim ofthe housing 904 for verifying cover placement. The optical sensorassembly 909 cooperates with a sensor-tripping structure (not shown) onthe cover 906 to verify that the cover is in place. Optical sensorassembly 909 preferably includes an Optek Technology, Inc. slottedoptical sensor, model number OPB980T11, available from Optek Technology,Inc. of Carrollton, Tex. The cover 906 also includes pipette openings908 through which pipette units 480, 482 can access reagent containerswithin the cooling bay 900.

[0337] The housing 904 is attached to a floor plate 910, and the floorplate 910 is attached to the datum plate 82 by means of suitablemechanical fasteners extending through openings formed in mountingflanges 911 spaced about the periphery of the floor plate 910. Coolingunits 912, preferably two, are attached to floor plate 910. Each coolingunit 912 comprises a thermoelectric module 914 attached cool-side-up tothe bottom surface of floor plate 910. Thermoelectric modules availablefrom Melcor, Inc. of Trenton, N.J., model number CP1.4-127-06L, providethe desired cooling capacity. A heat sink 916, including a plurality ofheat-dissipating fins 915, is attached to, or may be integral with, thebottom surface of floor plate 910, directly below the thermoelectricmodule 914. A fan unit 91100is attached in a position to drain heat awayfrom heat sink 916. Fan units 918 are preferably Orix fans, model numberMD825B-24, available from Oriental Motors Ltd. of Tokyo, Japan.Together, the cooling units 912 cool the interior of the housing 904 toa prescribed temperature for the benefit of temperature-sensitivereagents (e.g., enzymes) stored within the bay 900.

[0338] Two temperature sensors (only one temperature sensor 920 isshown) are disposed within the cooling bay 900 housing 904 formonitoring and controlling the interior temperature thereof. Thetemperature sensors are preferably thermistors (10 KOhm at 25° C.), andYSI 44036 series thermistors available from YSI, Inc. of Yellow Springs,Ohio are most preferred. YSI thermistors are preferred because of theirhigh accuracy and the ±0.1° C. interchangeability provided by YSIthermistors from one thermistor to another. One of the sensors is aprimary temperature control sensor, and the other is a temperaturemonitoring sensor. On the basis of the temperature indications from theprimary control sensor, the embedded controller adjusts power to thethermoelectric modules 914 and/or power to the fan units 91100to controlcooling bay temperature. The temperature monitoring sensor provides averification check of the primary temperature control sensor.

[0339] As shown in FIG. 38, container tray 922 is a one-piece turntablestructure with bottle-holding cavities 924 sized and shaped to receiveand hold specific reagent bottles 925. A drive system for container tray922 includes a motor 926, a small pulley 931 on the shaft of motor 926,a belt 928, a pulley 930, and a shaft 932. (a VEXTA stepper motor, modelnumber PK265-02A, available from Oriental Motor Co., Ltd. of Tokyo,Japan, and an SDP timing belt, GT® Series, available from SDP/SI of NewHyde Park, N.Y., are preferred). Motor 926 and cooling units 912 extendthrough openings (not shown) formed in the datum plate 82 and extendbelow the floor plate 910.

[0340] Container tray 922 may include a central, upstanding handle 923to facilitate installation of the tray 922 into and removal of the tray922 from the housing 904. A top portion 933 of shaft 932 extends throughfloor plate 910 and is received by a mating aperture (not shown) formedin the bottom of the tray 922. A sensor 940 extending up through thefloor plate 910 and into the housing 904 verifies that tray 922 is inplace within the housing 904. Sensor 940 is preferably a capacitiveproximity sensor available from Advanced Controls, Inc., of Bradenton,Fla., model number FCP2.

[0341] A position encoder 934 (preferably a slotted disk) in conjunctionwith an optical sensor 935 may be used to detect the position of thecontainer tray 922, so that a specific reagent bottle 925 may be alignedunder the pipette openings 908 in the cover 906.

[0342] As shown in FIG. 37, a preferred alternative to the positionencoder 934 and optical sensor 935 includes four slotted optical sensors937 (only two sensors are visible in FIG. 36) provided inside thehousing 904 along with a flag pin (not shown) extending from the bottomof container tray 922. One sensor is provided for each quadrant of thecontainer tray 922, and the flag trips one of the four sensors toindicate which quadrant of the container tray 922 is aligned with thepipette openings 908. Sensors 937 are preferably Optek Technology, Inc.sensors, model number OPB980T11, available from Optek Technology, Inc.of Carrollton, Tex.

[0343] A preferred alternative to the one-piece container tray 922 shownin FIG. 38 is a modular tray 1922 shown in FIGS. 35 and 39. Tray 1922includes a circular base plate 1926 and an upstanding handle post 1923attached to a central portion thereof. Modular pieces 1930 havingbottle-holding cavities 1924 are preferably connected to one another andto the base plate 1926 by pins 1928 and screws (not shown) to form thecircular tray 1922. Other means of securing the modular pieces 1930 maybe employed in the alternative to pins 1928 and screws. The modularpieces 1930 shown in the figures are quadrants of a circle, and thus, ofcourse, four such pieces 1930 would be required to complete the tray1922. Although quadrants are preferred, the modular pieces may howeverbe sectors of various sizes, such as, for example, {fraction (1/2)} of acircle or {fraction (1/8)} of a circle.

[0344] Alphanumeric bottle location labels 1940 are preferably providedon the base plate 1926 to identify positions within the tray 1922 forreagent containers. The preferred label scheme includes an encircledletter-number pair comprising a leading letter A, E, P, or S with atrailing number 1, 2, 3, or 4, The letters A, E, P, and S, designateamplification reagent, enzyme reagent, probe reagent, and selectreagent, respectively, corresponding to the preferred mode of use of theanalyzer 50, and the numbers 1-4 designate a quadrant of the tray 1922.Each modular piece 1930 includes a circular hole 1934 at the bottom ofeach bottle-holding cavity 1924. The holes 1934 align with the bottlelocation labels 1940, so that the labels 1940 can be seen when themodular pieces 1930 are in place on the base plate 1926.

[0345] The modular pieces 1930 of the container tray 1922 are configuredto accommodate reagent containers of different sizes corresponding toreagent quantities sufficient for performing two hundred fifty (250)assays or reagent quantities sufficient for performing five hundred(500) assays. Four 250-assay modular quadrants permit the reagentcooling bay to be stocked for 1000 assays, and four 500-assay modularquadrants permit the reagent cooling bay to be stocked for 2000 assays.Modular quadrants for 250 or 500 assay reagent kits can be mixed andmatched to configure the container tray for accommodating variousnumbers of a single assay type or various numbers of multiple differentassay types.

[0346] An insulation pad 938 is disposed between the container tray 922and the floor plate 910. Power, control, temperature, and positionsignals are provided to and from the reagent cooling bay 900 by aconnector 936 and a cable (not shown) linked to the embedded controllerof the analyzer 50.

[0347] A bar code scanner 941 is mounted to an upstanding scannermounting plate 939 attached to floor plate 910 in front of an opening942 formed in a side-wall of the cooling bay 900. The bar code scanner941 is able to scan bar code information from each of the reagentcontainers carried on the container tray 922. As shown in FIG. 39,longitudinal slots 1932 are formed along the bottle-holding cavities1924, and bar code information disposed on the sides of the reagentcontainer held in the bottle-holding cavities 1924 can be align with theslots 1932 to permit the bar code scanner 941 to scan the bar codeinformation. A preferred bar code scanner is available from Microscan ofNewbury Park, Calif. under model number FTS-0710-0001.

[0348] Pipette rinse basins 1942, 1944 are attached to the side of thehousing 904. Each rinse basin 1942, 1944 provides an enclosure structurewith a probe-receiving opening 1941, 1945, respectively, formed in a toppanel thereof and a waste drain tube 1946, 1948, respectively, connectedto a bottom portion thereof. A probe of a pipette unit can be insertedinto the rinse basin 1942, 1944 through the probe-receiving opening1941, 1945, and a wash and/or rinse fluid can be passed through theprobe and into the basin. Fluid in the rinse basin 1942, 1944 isconducted by the respective waste drain tube 1946, 1948 to theappropriate waste fluid container in the lower chassis 1100. In thepreferred arrangement and mode of operation of the analyzer 50, probe481 of pipette unit 480 is rinsed in rinse basin 1942, and probe 483 ofpipette unit 482 is rinsed in rinse basin 1944.

[0349] After the amplification reagent and oil are added to thereceptacle vessels 162 of MTU 160 in the left orbital mixer 552, theleft-side transport mechanism 502 retrieves the MTU 160 from the leftorbital mixer 552 and moves the MTU 160 to an available temperatureramp-up station 700 that is accessible to the left-side transportmechanism 502, i.e. on the left side of the chemistry deck 200, toincrease the temperature of the MTU 160 and its contents to about 60° C.

[0350] After sufficient ramp-up time in the ramp-up station 700, theleft-side transport mechanism 502 then moves the MTU 160 to the targetcapture and annealing incubator 600. The left-side distributor door 624of the target capture and annealing incubator 600 opens, and the MTUcarousel assembly 671 within the incubator 600 presents an empty MTUstation 676 to permit the left-side transport mechanism to insert theMTU into the incubator 600. The MTU 160 and its contents are thenincubated at about 60° C. for a prescribed incubation period. Duringincubation, the MTU carousel assembly 671 may continually rotate withinthe incubator 600 as other MTUs 600 are removed from and inserted intothe incubator 600.

[0351] Incubating at 60° C. in the annealing incubator 600 permitsdissociation of the capture probe/target nucleic acid hybridizationcomplex from the immobilized polynucleotide present in the assaysolution. At this temperature, oligonucleotide primers introduced fromthe reagent cooling bay 900 can hybridize to the target nucleic acid andsubsequently facilitate amplification of the target nucleotide basesequence.

[0352] Following incubation, the MTU carousel assembly 671 withinincubator 600 rotates the MTU 160 to the left-side distributor door 624,the left side distributor door 624 opens, and the left-side transportmechanism 502 retrieves the MTU 160 from the MTU carousel assembly 671of the target capture and annealing incubator 600. The left-sidetransport mechanism 502 then moves the MTU 160 to, and inserts the MTU160 into, an available temperature ramp-down station 700 that isaccessible to the left-side transport mechanism 502. The temperature ofthe MTU 160 and its contents is decreased to about 40° C. in theramp-down station. The MTU 160 is then retrieved from the ramp-downstation by the left-side transport mechanism 502 and is moved to theactive temperature and pre-read cool-down incubator 602. The left-sidedistributor door 624 of the AT incubator 602 opens, and the MTU carouselassembly 671 within incubator 602 presents an empty MTU station 676, sothat the left-side transport mechanism 502 can insert the MTU into theincubator 602. Within the active temperature and pre-read cool-downincubator 602, the MTU is incubated at about 41° C. for a period of timenecessary to stabilize the temperature of the MTU.

[0353] From the active temperature and pre-read cool-down incubator 602,the MTU is moved by transport mechanism 502 to the amplificationincubator 604 in which the temperature of the MTU is stabilized at 41.5°C. The MTU carousel assembly 671 within the amplification incubator 604rotates to place the MTU at the pipetting station below the pipetteopenings 662 formed in the cover 611 (see, e.g., FIG. 19). The containertray 922 within the reagent cooling bay 900 rotates to place the enzymereagent container below a pipette opening 908, and pipette unit 482 ofpipette assembly 470 transfers enzyme reagent from the reagent coolingbay 900 to each of the receptacle vessels 162 of the MTU 160.

[0354] As explained above, pipette units 480, 482 use capacitive levelsensing to ascertain fluid level within a container and submerge only asmall portion of the end of the probe 481, 483 of the pipette unit 480,482 to pipette fluid from the container. Pipette units 480, 482preferably descend as fluid is drawn into the respective probe 481, 483to keep the end of the probe submerged to a constant depth. Afterpipetting reagent into the pipette unit 480 or 482, the pipette unitcreates a minimum travel air gap of 10 μl in the end of the respectiveprobe 481 or 483 to ensure no drips fall from the end of the probe.

[0355] After enzyme reagent is added to each receptacle vessel 162, theMTU carousel assembly 671 of amplification incubator 604 rotates MTU 160to the skewed disk linear mixer 634 within amplification incubator 604and the MTU 160 and its contents are mixed as described above at about10 Hz to facilitate exposure of the target nucleic acid to the addedenzyme reagent. The pipette unit 482 is moved to rinse basin 1942, andthe probe 483 is rinsed by passing distilled water through it.

[0356] The MTU 160 is then incubated within amplification incubator 604at about 41.5° C. for a prescribed incubation period. The incubationperiod should be sufficiently long to permit adequate amplification ofat least one target nucleotide base sequence contained in one or moretarget nucleic acids which may be present in the receptacle tubes 162.Although the preferred embodiment is designed to facilitateamplification using a transcription-mediated amplification (TMA)procedure, which is discussed in the background section supra,practitioners will easily appreciate those modifications necessary toperform other amplification procedures using the analyzer 50. Inaddition, an internal control sequence is preferably added at thebeginning of the assay to provide confirmation that the amplificationconditions and reagents were appropriate for amplification. Internalcontrols are well known in the art and require no further discussionhere.

[0357] Following amplification incubation, the MTU 160 is moved by theleft-side transport mechanism 502 from the amplification incubator 604to an available ramp-up station 700 that is accessible to the left-sidetransport mechanism 502 to bring the temperature of the MTU 160 and itscontents to about 60° C. The MTU 160 is then moved by the left-sidetransport mechanism 502 into the hybridization incubator 606. The MTU160 is rotated to a pipetting station in the hybridization incubator606, and a probe reagent from the reagent cooling bay 900 is pipettedinto each receptacle vessel, through openings 662 in the cover 611 ofthe hybridization incubator 606, by the pipette unit 480. The probereagent includes chemiluminescent detection probes, and preferablyacridinium ester (AE)-labeled probes which can be detected using ahybridization protection assay (HPA). Acridinium ester-labeled probesand the HPA assay are well known in the art and are described more fullyin the background section supra. While AE-labeled probes and the HPAassay are preferred, the analyzer 50 can be conveniently adapted toaccommodate a variety of detection methods and associated probes, bothlabeled and unlabeled. Confirmation that detection probe has been addedto the receptacle vessels 162 can be accomplished using an internalcontrol that is able (or its amplicon is able) to hybridize to a probein the probe reagent, other than the detection probe, under the HPAassay conditions extant in the receptacle vessels 162 in thehybridization incubator 606. The label of this probe must bedistinguishable from the label of the detection probe.

[0358] After dispensing probe reagent into each of the receptaclevessels 162 of the MTU 160, the pipette unit 480 moves to the pipetterinse basin 1944, and the probe 481 of the pipette unit is rinsed withdistilled water.

[0359] The MTU carousel assembly 671 rotates the MTU 160 to the skeweddisk linear mixer 634 where the MTU 160 and its contents are mixed, asdescribed above, at about 14 Hz to facilitate exposure of the targetamplicon to the added detection probes. The MTU 160 is then incubatedfor a period of time sufficient to permit hybridization of the detectionprobes to the target amplicon.

[0360] After hybridization incubation, the MTU 160 is again rotatedwithin incubator 606 by the MTU carousel assembly 671 to the pipettingposition below the pipette openings 662. A selection reagent stored in acontainer in the reagent cooling bay 900 is pipetted into eachreceptacle vessel 162 by the pipette unit 480. A selection reagent isused with the HPA assay and includes an alkaline reagent thatspecifically hydrolyzes acridinium ester label which is associated withunhybridized probe, destroying or inhibiting its ability tochemiluminesce, while acridinium ester label associated with probehybridized to target amplicon (or amplicon of the internal standard) isnot hydrolyzed and can chemiluminesce in a detectable manner underappropriate detection conditions.

[0361] Following addition of the selection reagent to each of thereceptacle vessels 162 of the MTU 160, the pipette probe 481 of thepipette unit 480 is rinsed with distilled water at the pipette rinsebasin 1944. The MTU 160 is rotated by the MTU carousel assembly 671within the incubator 606 to the skewed disk linear mixer 634 and mixed,as described above, at about 13 Hz to facilitate exposure of the targetamplicon to the added selection reagent. The MTU is then incubated inthe incubator 606 for a period of time sufficient to complete theselection process.

[0362] After selection incubation is complete, the left-side transportmechanism 502 transfers the MTU 160 into an available ramp-down station700 that is accessible to the left-side transport mechanism 502 to coolthe MTU 160. After the MTU 160 is cooled, it is retrieved from theramp-down station by the left-side transport mechanism 502 and is movedby the transport mechanism 502 into the active temperature and pre-readcool-down incubator 602 to stabilize the temperature of the MTU 160 atabout 40° C.

[0363] When a period sufficient to stabilize the temperature of the MTU160 has passed, the MTU carousel assembly 671 within active temperatureand pre-read cool-down incubator 602 rotates to present the MTU 160 atthe right-side distributor door of the incubator 602. The right-sidedistributor door 622 is opened and the MTU 160 is removed from activetemperature and pre-read cool-down incubator 602 by right-side transportmechanism 500.

[0364] The right-side transport mechanism 500 moves the MTU to a barcode scanner (not shown) which scans MTU bar code information posted onthe label-receiving surface 175 of the label-receiving structure 174 ofthe MTU 160. The bar code scanner is preferably attached to an outerwall of the housing of the luminometer 950. A preferred bar code scanneris available from Opticon, Inc., of Orangeburg, N.Y., as part numberLHA1127RR1S-032. The scanner verifies the total time of assay prior toentering the luminometer 950 by confirming the correct MTU at thecorrect assay time. From the bar code reader, the right-side transportmechanism 500 moves the MTU 160 to the luminometer 950.

[0365] In a preferred mode of operation, before the right-side transportmechanism 500 moves the MTU 160 into the luminometer 950, the MTU 160 isplaced by the right-side transport mechanism 500 into an available MTUramp-down station, or chiller, to decrease the temperature of the MTU160 to 24±320 C. It has been determined that the MTU contents exhibit amore consistent chemiluminescent “light-off” at this cooler temperature.

[0366] Luminometer

[0367] Referring to FIGS. 40-42C, a first embodiment of the luminometer950 includes an electronics unit (not shown) within a housing 954. Aphotomultiplier tube (PMT) 956 linked to the electronics unit extendsfrom within the housing 954 through a PMT plate 955, with the front endof the PMT 956 aligned with an aperture 953. A preferred PMT isavailable from Hamamatsu Corp. of Bridgewater, N.J. as model number HC135. Signal measurements using the preferred PMT are based on the wellknown photon counter system.

[0368] The aperture 953 is centered in an aperture box 958 in front ofthe PMT plate 955. The aperture 953 and aperture box 958 are entirelyenclosed by a housing, defined by a floor plate 964, a top plate 966,the PMT plate 955, and a back frame 965 and back plate 967, whichprevents stray light from entering the aperture 953 and which isattached to the datum plate 82. An MTU transport path extends throughthe housing in front of the aperture 953, generally transversely to anoptical axis of the aperture. MTUs 160 pass through the luminometer 950via the MTU transport path. A back rail 991 and a front rail 995 aredisposed on opposite sides of the MTU transport path and provideparallel horizontal flanges which support the connecting rib structure164 of an MTU 160 disposed within the luminometer 950. Revolving doors960 are supported for rotation within associated door housings 961disposed on opposite ends of the MTU transport path and are turned bydoor motors 962, which may comprise stepper motors or DC gear motors.

[0369] The door housings 961 provide openings through which MTUs 160 canenter and exit the luminometer 950. An MTU 160 enters the luminometer950 by means of the right-side transport mechanism 500 inserting the MTU160 through one of the door housings 961. The MTU 160 exits theluminometer under the influence of an MTU transport assembly, variousembodiments of which are described below, which moves MTUs through theMTU transport path and eventually out of the luminometer through theother door housing 961.

[0370] Revolving doors 960 are generally cylindrical and include acut-out portion 963. Each revolving door 960 can be rotated between anopen position, in which the cut-out portion 963 is generally alignedwith the opening of the associated door housing 961, so that an MTU 160can pass through the opening, and a closed position, in which a side ofthe revolving door opposite the cut-out portion 963 extends across theopening of the associated door housing 961 so that neither an MTU 160nor light can pass through the opening. Except when an MTU 160 isentering or exiting the luminometer 950, the revolving doors 960 arepreferably in their respective closed positions to prevent stray lightfrom entering the luminometer. Because test results are ascertained bythe amount of light detected by the PMT 956, stray light from sourcesother than the receptacle 160 being sampled can cause erroneous results.

[0371] As shown in FIGS. 40-42C, the MTU transport assembly may includean MTU advance motor 972 which drives a lead screw 974 through a timingbelt (not shown) or bevel gears (not shown). A screw follower 976engaged to the lead screw 974 is coupled to an MTU bracket 977 extendingaway from lead screw 974 to engage the MTU 160. The MTU bracket 977 hasa guide flange 978 with an elongated, slightly arcuate guide hole 979formed therein. A guide rod 980 extends through the luminometer 950adjacent and parallel to the lead screw 974. Guide rod 980 extendsthrough guide hole 979.

[0372] To advance the MTU bracket 977 (from bottom to top in FIG. 42C),the lead screw 974 turns counter-clockwise, as viewed in FIG. 42B. Dueto system friction, the screw follower 976 and the MTU bracket 977 willalso turn counter-clockwise with the lead screw 974 until the guide rod980 contacts the left-side of the guide hole 979. When guide rod 980contacts the side of guide hole 979, MTU bracket 977 and screw follower976 can no longer rotate with lead screw 974, and further rotation ofthe lead screw 974 will cause the MTU bracket 977 and screw follower 976to advance along the lead screw 974. Arms 981 extending from the MTUbracket 977 will also rotate counter-clockwise over a limited arc toengage the MTU 160 and advance it through the luminometer 950, as thelead screw 974 rotates.

[0373] After the MTU 160 has passed the PMT 956, that MTU is ejectedfrom the luminometer 950 and the next MTU can be pulled through theluminometer 950. The MTU bracket 977 moves toward the MTU entrance endof the MTU transport path by clockwise rotation of the lead screw 974.System friction will cause the screw follower 976 and MTU bracket 977 torotate clockwise until the guide rod 980 contacts the right-side ofguide opening 979, after which, continued rotation of the lead screw 974will cause the screw follower 976 and the MTU bracket 977 to retreatalong the lead screw 974. This clockwise movement of the MTU bracket 977will cause the arms 981 to rotate clockwise over a limited arc todisengage from the MTU, so the MTU bracket 977 can retreat withoutcontacting the MTU. That is, the arms 981 will pass over the top of theMTU as the MTU bracket 977 retreats

[0374] As shown in FIG. 41, a blinder 982, driven by a blinder actuator993, moves vertically up and down, in alignment with the aperture 953.Blinder 982 includes a front panel 983 which is mounted for slidingmovement with respect to the aperture box 958 and which includes agenerally rectangular opening (not shown) formed therein which can bealigned with the aperture 953. A top portion of the front panel 983blocks the aperture 953 when the opening formed in panel 983 is notaligned with the aperture 953 and thus operates as a shutter for theaperture 953. The blinder 982 includes two side-walls 987, arranged inparallel on opposite sides of the opening and generally perpendicular tothe front panel 983, and a back wall 988 spanning the back edges of thesidewalls 987 opposite the front wall 983 and generally parallel to thefront wall 983. The side-walls 987 and the back wall 988 define apartial rectangular enclosure sized to accommodate one receptacle vessel162 of the MTU 160 when the blinder 982 is moved up beneath one of thereceptacle vessels 162 of an MTU 160 by the blinder actuator 993.Blinder actuator 993 may be a linear stepper actuator including astepper motor 992 and a lead screw 994. HSI linear stepper actuators,available from Haydon Switch and Instrument, Inc. of Waterbury, Conn.have been used.

[0375] After the MTU 160 is placed into the luminometer 950 by theright-side transport mechanism 500, the motor 972 is energized to pullthe first receptacle vessel of the MTU into alignment with the aperture953. The blinder 982, which is normally stowed out of the MTU transportpath, is raised by the blinder actuator 993 until the side walls 987 andback wall 988 of the blinder 982 surround the receptacle vessel 162 andthe opening formed in the front panel 983 of the blinder 982 is alignedwith the aperture 953. The blinder 982 substantially prevents light fromsources other than the receptacle vessel 162 in front of the aperture953 from reaching the aperture 953, so that the PMT 956 detects onlylight emissions from the receptacle vessel directly in front of theaperture 953.

[0376] With the PMT shutter open, different detecting reagents (Detect Iand Detect II), drawn from containers 1146, 1170 of the lower chassis1100, are sequentially delivered into the aligned receptacle vessel 162through dedicated delivery lines (not shown) extending to a reagent port984 at the top of the luminometer 950. The Detect I and Detect IIreagents are hydrogen peroxide-containing and sodiumhydroxide-containing reagents, respectively, and combine to form a basichydrogen peroxide solution which enhances the chemiluminescence ofacridinium ester label which has not been hydrolyzed. Because basichydrogen peroxide is unstable, the Detect I and Detect II reagents arepreferably combined in the receptacle tube 162 just prior to detectionin the luminometer 950.

[0377] After the addition of Detect II, the light emitted from thecontents of the receptacle vessel 162 is detected using the PMT 956 andthe PMT shutter is then closed. The PMT 956 converts light emitted bychemiluminescent labels into electrical signals processed by theelectronics unit and thereafter sent to the controller 1000 or otherperipheral unit via cables (not shown) linked to a connector 986.

[0378] In cases where less sensitivity is required, it may be possibleto use an optical sensor in place of a photomultiplier tube. A diode isan example of an acceptable optical sensor which can be used with theluminometer 950. An optical sensor may also be appropriate when thematerial of the MTU 160 is relatively transparent, rather than thetranslucent appearance of the preferred polypropylene material. Whenselecting a material for the MTU 160, care should be taken to avoidmaterials that naturally luminesce or are predisposed to electrostaticbuild-up, either of which can increase the chances of a false positiveor interfering with quantification measurements.

[0379] The above-described process is repeated for each receptaclevessel 162 of the MTU 160. After the chemiluminescent signal from eachreceptacle vessel 162 of the MTU 160 has been measured, the motor 972advances to move the MTU 160 through the exit door 961 and out of theluminometer 950 and into the amplicon deactivation station 750.

[0380] An alternate, and presently preferred, luminometer is generallydesignated by reference number 1360 in FIG. 43. Luminometer 1360includes a housing 1372 having a bottom wall 1370, door assemblies 1200on opposite sides of the bottom wall 1370 which define end portions ofthe housing 1372, an optical sensor shutter assembly 1250 which definesa front wall of the housing 1370, a top wall (not shown), and a backwall (not shown), which complete the housing 1370 and define anenclosure therein. The right-side door assembly 1200 defines areceptacle entrance opening 1374, and the left-side door assembly 1200defines a receptacle exit opening 1376 through which a MTU 160 can bepassed into and out of the housing 1370. Each door assembly 1200controls access through the respective opening 1374 or 1376 andcomprises an end wall 1202, a cover plate 1232, and a rotating door 1220rotatably disposed between the end wall 1202 and the cover plate 1232.The optical sensor aperture shutter assembly 1250 controls lightentering an optical sensor (not shown in FIG. 43), for example aphotomultiplier tube. Luminometer 1360 includes a light receivermounting wall 1250 and a cover plate 1290 having an aperture 1292 formedtherein.

[0381] A bar code scanner 1368 is attached to a front portion of thehousing 1372 for scanning MTUs prior to their entry to the luminometer1360.

[0382] A receptacle transport assembly 1332 moves a receptacle (e.g., aMTU 160) through the luminometer 1360 from the entrance opening 1374 tothe exit opening 1376. The assembly 1332 includes a transport 1342movably carried on a threaded lead screw 1340 that is rotated by a motor1336 coupled to the lead screw 1340 by a belt (not shown).

[0383] A dispensing nozzle 1362 is attached in the top wall (not shown)and is connected by conduit tubes 1364 and 1366 to a pump and ultimatelyto bottles 1146 and 1170 in the lower chassis 1100. Nozzle 1362dispenses the “Detect I” and the “Detect II” reagents into thereceptacles 162 of the MTU 160 within the housing 1372.

[0384] A receptacle vessel positioner assembly 1300 is disposed withinthe housing 1372 and is constructed and arranged to position each tube162 of the MTU 160 in front of the aperture 1292 and to opticallyisolate each tube being positioned from adjacent tubes, so that onlylight from one tube at a time enters the aperture 1292. The positionerassembly 1300 comprises a receptacle positioner 1304 rotatably mountedwithin a positioner frame 1302 that is secured to the floor 1370 of thehousing 1372.

[0385] The door assembly 1200 for the MTU entrance opening 1374 and exitopening 1376 of the luminometer 1360 is shown in FIG. 44. Door assembly1200 includes a luminometer end-wall 1202 which forms an end wall of theluminometer housing 1372. End-wall 1202 includes a first recessed area1206 with a second, circular recessed area 1208 superimposed on thefirst recessed area 1206. A circular groove 1207 extends about theperiphery of the circular recessed area 1208. A slot 1204, having ashape generally conforming to a longitudinal profile of an MTU 160, isformed in the circular recessed area 1208 to one side of the centerthereof. A short center post 1209 extends from the center of thecircular recessed area 1208.

[0386] The rotating door 1220 is circular in shape and includes an axialwall 1222 extending about the periphery of the rotating door 1220. Theaxial wall 1222 is disposed a short radial distance from the outerperipheral edge of the rotating door 1220, thus defining an annularshoulder 1230 about the outermost peripheral edge outside the axial wall1222. A slot 1226, having a shape generally conforming to thelongitudinal profile of an MTU is formed in the rotating door 1220 at anoff-center position.

[0387] The rotating door 1220 is installed into the circular recessedarea 1208 of the end-wall 1202. A central aperture 1224 receives thecenter post 1209 of the end-wall 1202, and circular groove 1207 receivesaxial wall 1222. The annular shoulder 1230 rests on the flat surface ofthe recessed area 1206 surrounding the circular recessed area 1208.

[0388] End-wall 1202 includes a drive gear recess 1210 which receivestherein a drive gear 1212 attached to the drive shaft of a motor 1213(See FIG. 43 in which only the motor 1213 for the right side doorassembly 1200 is shown). Motor 1213 is preferably a DC gear motor. Apreferred DC gear motor is available from Micro Mo Electronics, Inc. ofClearwater, Fla., under model number 1524TO24SR 16/7 66:1. The outercircumference of the axial wall 1222 of the rotating door 1220 has gearteeth formed thereon which mesh with the drive gear 1212 when theshutter is installed into the circular recess 1208.

[0389] The cover plate 1232 is generally rectangular in shape andincludes a raised area 1234 having a size and shape generally conformingto the recessed area 1206 of the end-wall 1202. Cover plate 1232 hasformed therein an opening 1236 having a shape generally conforming tothe longitudinal profile of an MTU, and, when the cover plate 1232 isinstalled onto the end-wall 1202, the raised rectangular area 1234 isreceived within the rectangular recessed area 1206 and opening 1236 isin general alignment with opening 1204. Thus, the rotating door 1220 issandwiched between the cover plate 1232 and the end-wall 1202, and theopenings 1236 and 1204 together define the entrance opening 1374 andexit opening 1376.

[0390] When the drive gear 1212 is rotated by the motor 1213, therotating door 1220, enmeshed with the drive gear 1212, is caused torotate about the center post 1209. When the opening 1226 is aligned withopenings 1204 and 1236, MTUs 160 can be passed through the opening 1374(1376) of the door assembly 1200. With the rotating door 1220 disposedwithin the circular recessed area 1208 and the raised area 1234 of thecover plate 1232 disposed within the recessed area 1206 of the end-wall1202, a substantially light-tight structure is achieved, whereby littleor no light enters through the door, when the opening 1226 is notaligned with openings 1204 and 1236.

[0391] Optical slotted sensors are disposed within slots 1214 and 1216disposed on the outer edge of the circular recessed area 1208 atdiametrically opposed positions. Preferred sensors are available fromOptek Technology, Inc. of Carrollton, Tex., model number OPB857. Theslotted sensors disposed within slots 1214 and 1216 detect the presenceof a notch 1228 formed in the axial wall 1222 to signal door open anddoor closed status.

[0392] The optical sensor aperture shutter assembly 1250 is shown inFIG. 45. A light receiver, such as a photomultiplier tube 956, iscoupled with a light receiver opening 1254 formed in a light receivermounting wall 1252. The light receiver mounting wall 1252 includes agenerally rectangular, two-tiered raised area 1256, which defines agenerally rectangular shoulder 1257 and a circular recessed area 1258superimposed on the rectangular raised area 1256. A circular groove 1261extends about the periphery of circular recessed area 1258. A centerpost 1259 is positioned at the center of the circular recessed area1258. Light receiver opening 1254 is formed in the circular recessedarea 1258. In the illustrated embodiment, the light receiver opening1254 is disposed below the center post 1259, but the light receiveropening 1254 could be placed at any position within the circularrecessed area 1258.

[0393] The aperture shutter assembly 1250 includes a rotating shutter1270 having an axial wall 1274 with gear teeth formed on the outerperiphery thereof Axial wall 1274 is formed near, but not at, the outerperiphery of the shutter 1270, thereby defining annular shoulder 1276.Rotating shutter 1270 is installed in the circular recessed area 1258with center post 1259 received within a central aperture 1272 formed inthe rotating shutter 1270 and with axial wall 1274 received withincircular groove 1261. A drive gear 1262 disposed within a gear recess1260 and coupled to a drive motor 1263 meshes with the outer gear teethformed on the axial wall 1274 of the rotating shutter 1270 to rotate therotating shutter 1270 about the center post 1259. A preferred drivemotor 1263 is a DC gear motor available from Micro Mo Electronics, Inc.of Clearwater, Fla., as model number 1524TO24SR 16/7 66:1. Micro Mo gearmotors are preferred because they provide a high quality, low backlashmotor. An opening 1280 is formed in the rotating shutter 1270 which canbe moved into and out of alignment with light receiver opening 1254 asthe rotating shutter 1270 is rotated.

[0394] With the shutter 1270 installed in the circular recessed area1258, a cover plate, or sensor aperture wall, 1290 is installed onto thesensor mount 1252. As shown in FIG. 45A, sensor aperture wall 1290includes a generally rectangular, two-tiered recessed area 1296 whichdefines a generally rectangular shoulder 1297 and which is sized andshaped to receive therein the rectangular raised area 1256 of the sensormount 1252. A sensor aperture 1292 is formed through the aperture wall1290 and is generally aligned with the light receiver opening 1254formed in the sensor mount 1252. The sensor aperture 1292 is generallyin the shape of an elongated oval having a width generally correspondingto the width of an individual receptacle vessel 162 of an MTU 160 and aheight corresponding to the height of the intended viewing area.Although opening 1280 of shutter 1270 is shown in the illustratedembodiment to be circular, opening 1280 can have other shapes, such asrectangular, with a width corresponding to the width of a receptaclevessel 162 or an elongated oval similar to sensor aperture 1292.Rotation of the rotating shutter 1270 to a position in which the opening1280 is aligned with the light receiver opening 1254 and the sensoraperture 1292 permits light to reach the PMT 956, and rotation of therotating shutter 1270 to a position in which the opening 1280 is notaligned with light receiver opening 1254 and sensor aperture 1292prevents light from reaching the PMT 956.

[0395] Slotted optical sensors are disposed in slots 1264 and 1266 anddetect a notch 1278 formed in the axial wall 1274 of the shutter 1270 todetect opened and closed positions of the shutter 1270. Preferredslotted optical sensors are available from Optek Technology, Inc., ofCarrollton, Tex., as model number OPB857.

[0396] The aperture wall 1290 includes an upwardly facing shoulder 1294extending across the width thereof. A downwardly facing shoulder of theMTU 160, defined by the connecting rib structure 164 of the MTU 160 (seeFIG. 58), is supported by the shoulder 1294 as the MTU 160 slidesthrough the luminometer.

[0397] The receptacle vessel positioner assembly 1300 is shown in FIGS.46 and 48-49. The receptacle vessel positioner 1304 is operativelydisposed within the receptacle vessel positioner frame 1302. Thereceptacle vessel positioner 1304 is mounted in the receptacle vesselpositioner frame 1302 for rotation about a shaft 1308. Shaft 1308 isoperatively coupled to a rotary solenoid, or, more preferably, a gearmotor 1306, to selectively rotate the receptacle vessel positioner 1304between the retracted position shown in FIG. 46 and the fully extendedposition shown in FIG. 48. A preferred gear motor drive is availablefrom Micro Mo Electronics, Inc. of Clearwater, Fla., as model number1724T024S+16/7 134:1+X0520.

[0398] As shown in FIG. 47, the receptacle vessel positioner 1304includes a V-block structure 1310 defining two parallel walls 1312.Receptacle vessel positioner 1304 further includes an area at the lowerend thereof where a portion of the thickness of the receptacle vesselpositioner 1304 is removed, thus defining a relatively thin arcuateflange 1314.

[0399] When an MTU 160 is inserted into the luminometer 1360, thereceptacle vessel positioner 1304 is in the retracted position shown inFIG. 46. When an individual receptacle vessel 162 is disposed in frontof the sensor aperture 1292 (see FIG. 45A), so that a sensor reading ofthe chemiluminescence of the contents of the receptacle vessel 162 canbe taken, the receptacle vessel positioner 1304 rotates forwardly to theengaged position shown in FIG. 49. In the engaged position shown in FIG.49, the V-block 1310 engages the receptacle vessel 162, thus holding thereceptacle vessel in the proper position in alignment with the lightreceiver aperture 1292 of the luminometer. As shown in FIG. 45, aperturewall 1290 includes a protrusion 1298 extending from the back of wall1290 into the MTU passage of the luminometer. The protrusion 1298 isaligned with the aperture 1292 so that when the receptacle vesselpositioner 1304 engages a receptacle vessel 162, the receptacle vesselis pushed laterally and encounters protrusion 1298 as a hard stop, thuspreventing the receptacle vessel positioner 1304 from significantlytilting the receptacle vessel 162 within the MTU passage. The parallelsidewalls 1312 of the V-block 1310 prevent stray light from adjacentreceptacle vessels 162 of the MTU 160 from reaching the light receiverwhile a reading is being taken of the receptacle vessel 162 disposeddirectly in front of the aperture 1292.

[0400] A slotted optical sensor 131100is mounted to a lower portion ofthe frame 1302, with the arcuate flange 1314 operatively positioned withrespect to the sensor 1318. A preferred slotted optical sensor isavailable from Optek Technology, Inc., of Carrollton, Tex., as modelnumber OPB930W51. An opening 1316 is formed in the flange 1314. Opening1316 is properly aligned with the sensor 131100when the receptaclevessel positioner 1304 engages a receptacle vessel 162 and thereceptacle vessel 162 and protrusion 1298 prevent further rotation ofthe receptacle vessel positioner 1304. If a receptacle vessel 162 is notproperly positioned in front of the receptacle vessel positioner 1304,the receptacle vessel positioner 1304 will rotate forwardly to theposition shown at FIG. 48, in which case opening 1316 will not bealigned with the sensor 1318 and an error signal will be generated.

[0401] If a gear motor 1306 is employed for rotating the receptaclevessel positioner 1304, it is necessary to provide a second sensor (notshown) to generate a positioner-retracted, i.e., “home”, signal to shutoff the gear motor when the receptacle vessel positioner 1304 is fullyretracted, as shown in FIG. 46. A preferred sensor is available fromOptek Technology, Inc. of Carrollton, Tex. as model number OPB900W.

[0402] The MTU transport assembly 1332 is shown in FIG. 50. The MTUtransport assembly 1332 is operatively positioned adjacent a top edge ofan intermediate wall 1330 (not shown in FIG. 43) of the luminometer1360. Intermediate wall 1330, which defines one side of the MTUtransport path through the luminometer housing 1372, includes arectangular opening 1334. The receptacle vessel positioner frame 1302(see, e.g., FIG. 48) is mounted to the intermediate wall 1330 proximatethe opening 1334, and the receptacle vessel positioner 1304 rotates intoengagement with an MTU 160 through the opening 1334.

[0403] The MTU transport 1342 is carried on the threaded lead screw 1340and includes a screw follower 1344 having threads which mesh with thethreads of the lead screw 1340 and an MTU yoke 1346 formed integrallywith the screw follower 1344. As shown in FIG. 51, the MTU yoke 1346includes a longitudinally-extending portion 1356 and twolaterally-extending arms 1348 and 1350, with a longitudinal extension1352 extending from the arm 1350. The lead screw 1340 is driven, via adrive belt 1338, by the stepper motor 1336. A preferred stepper motor isa VEXTA motor, available from Oriental Motors Ltd. of Tokyo, Japan,model PK266-01A, and a preferred drive belt is available from SDP/SI ofNew Hyde Park, N.Y.

[0404] When an MTU 160 is inserted into the MTU transport path of theluminometer 950 by the right-side transport mechanism 500, the firstreceptacle vessel 162 of the MTU 160 is preferably disposed directly infront of the sensor aperture 1292 and is thus properly positioned forthe first reading. The width of the yoke 1346 between the lateral arms1348 and 1350 corresponds to the length of a single MTU 160. Thetransport 1342 is moved between a first position shown in phantom inFIG. 50 and a second position by rotation of the lead screw 1340.Slotted optical sensors 1341 and 1343 respectively indicate that thetransport 1342 is in the either the first or second position. Due tofriction between the lead screw 1340 and the screw follower 1344, theMTU transport 1342 will have a tendency to rotate with the lead screw1340. Rotation of the MTU transport 1342 with the lead screw 1340 ispreferably limited, however, to 12 degrees by engagement of a lowerportion of the yoke 1346 with the top of the intermediate wall 1330 andengagement of an upper stop 1354 with the top cover (not shown) of theluminometer housing 1372.

[0405] To engage the MTU that has been inserted into the luminometer1360, the lead screw 1340 rotates in a first direction, and frictionwithin the threads of the screw follower 1344 and the lead screw 1340causes the transport 1342 to rotate with lead screw 1340 upwardly untilthe upper stop 1354 encounters the top cover (not shown) of theluminometer 1360. At that point, continued rotation of the lead screw1340 causes the transport 1342 to move backward to the position shown inphantom in FIG. 50. The lateral arms 1348, 1350 pass over the top of theMTU as the transport 1342 moves backward. Reverse rotation of the leadscrew 1340 first causes the transport 1342 to rotate downwardly with thelead screw 1340 until a bottom portion of the yoke 1346 encounters thetop edge of the wall 1330, at which point the lateral arms 1348 and 1350of the yoke 1346 straddle the MTU 160 disposed within the luminometer1360.

[0406] The MTU transport mechanism 1332 is then used to incrementallymove the MTU 160 forward to position each of the individual receptaclevessels 162 of the MTU 160 in front of the optical sensor aperture 1292.After the last receptacle vessel 162 has been measured by the lightreceiver within the luminometer, the transport 1342 moves the MTU 160 toa position adjacent the exit door, at which point the lead screw 1340reverses direction, thus retracting the transport 1342 back, asdescribed above, to an initial position, now behind the MTU 160.Rotation of the lead screw 1340 is again reversed and the transport 1342is then advanced, as described above. The exit door assembly 1200 isopened and the longitudinal extension 1352 of the yoke 1346 engages theMTU manipulating structure 166 of the MTU 160 to push the MTU 160 out ofthe luminometer exit door and into the deactivation queue 750.

[0407] Deactivation Station

[0408] In the amplicon deactivation station 750, dedicated deliverylines (not shown) add a deactivating solution, such as buffered bleach,into the receptacle vessels 162 of the MTU 160 to deactivate theremaining fluid in the MTU 160. The fluid contents of the receptaclevessels are aspirated by tubular elements (not shown) connected todedicated aspiration lines and collected in a dedicated liquid wastecontainer in the lower chassis 1100. The tubular elements preferablyhave a length of 4.7 inches and an inside diameter of 0.041 inches.

[0409] An MTU shuttle (not shown) moves the MTUs 160 incrementally (tothe right in FIG. 3) with the delivery of each subsequent MTU 160 intothe deactivation station 750 from the luminometer 950. Before an MTU canbe delivered to the deactivation queue 750 by the luminometer 950, theMTU shuttle must be retracted to a home position, as sensed by astrategically positioned optical slot switch. After receiving an MTU 160from the luminometer, the shuttle moves the MTU 160 to a deactivationstation where the dedicated delivery lines connected to dedicatedinjectors dispense the deactivating solution into each receptacle vessel162 of the MTU 160. Previous MTUs in the deactivation queue, if any,will be pushed forward by the distance moved by the MTU shuttle. Sensorsat the deactivation station verify the presence of both the MTU and theMTU shuttle, thus preventing the occurrence of a deactivating fluidinjection into a non-existent MTU or double injection into the same MTU.

[0410] An aspiration station (not shown) includes five, mechanicallycoupled aspirator tubes mounted for vertical movement on an aspiratortube rack and coupled to an actuator for raising and lowering theaspirator tubes. The aspiration station is at the last position alongthe deactivation queue before the MTUs are dropped through a hole in thedatum plate 82 and into the waste bin 1108. Each time an MTU moves intothe deactivation station, the aspirator tubes cycle up and down onetime, whether an MTU is present in the aspiration station or not. If anMTU is present, the aspirator tubes aspirate the fluid contents from theMTU. When the next MTU is moved into the deactivation station by the MTUshuttle, the last-aspirated MTU is pushed off the end of thedeactivation queue and falls into the waste bin 1108.

[0411] The steps and sequence of the above-described assay procedureperformed on the analyzer 50 in the preferred mode of operation aregraphically and succinctly described in the document Gen-Probe TIGRISStoryboard v. 1.0, Jun. 23, 1997, a copy of which was filed with theprovisional disclosure upon which priority is claimed for the presentspecification and the contents of which are hereby incorporated byreference.

[0412] Ideally, the analyzer 50 can run about 500 preferred assays in an8 hour period, or about 1,000 preferred assays in a 12 hour period. Oncethe analyzer 50 is setup and initialized, it ordinarily requires littleor no operator assistance or intervention. Each sample is handledidentically for a given assay, although the analyzer is capable ofsimultaneously performing multiple assay types in which different MTUsmay or may not be handled identically. Consequently, manual pipetting,incubation timing, temperature control, and other limitations associatedwith manually performing multiple assays are avoided, thereby increasingreliability, efficiency, and throughput. And because an operator'sexposure to samples is generally limited to the loading of samples,risks of possible infection are greatly reduced.

[0413] While the invention has been described in connection with whatare presently considered to be the most practical and preferredembodiments, it is to be understood that the invention is not to belimited to the disclosed embodiments, but, on the contrary, is intendedto cover various modifications and equivalent arrangements includedwithin the spirit and scope of the appended claims.

[0414] Furthermore, those of the appended claims which do not includelanguage in the “means for performing a specified function” formatpermitted under 35 U.S.C. §112(¶6), are not intended to be interpretedunder 35 U.S.C. §112(¶6) as being limited to the structure, material, oracts described in the present specification and their equivalents.

What is claimed is:
 1. A device for agitating the fluid contents of atleast one container, said device comprising: a turntable structureconstructed and arranged to be rotatable about a first axis of rotation;one or more container holders, each of said container holders having anaxis of rotation and being constructed and arranged to hold a containertherein, said container holders being mounted on said turntablestructure so as to be rotatable therewith and so that said axis ofrotation of each container holder is generally parallel to said firstaxis of rotation; a container holder mounting assembly associated witheach container holder, said container holder mounting assembly beingconstructed and arranged to mount said associated container holder tosaid turntable structure and to permit said associated container holderto rotate about a second axis of rotation that is generally parallel toand spaced from both said first axis of rotation and said axis ofrotation of said associated container holder; and rotational motioncoupling elements operatively associated with said turntable structureand said container holder mounting structure and constructed andarranged to cause each container holder to rotate about said second axisof rotation as said turntable structure rotates about said first axis ofrotation.
 2. The device of claim 1 further comprising four containerholders spaced 90 degrees from each other.
 3. The device of claim 1,wherein said turntable structure is in the form of a right angle crosscomprising four 90 degree-spaced arms extending radially from said firstaxis of rotation.
 4. The device of claim 3, wherein three of said fourarms are of generally the same length and a fourth arm is longer thanthe other three arms.
 5. The device of claim 3 further comprising fourcontainer holders, each of said container holders being mounted on anassociated one of said arms of said turntable structure, and all of saidcontainer holders being mounted on said turntable structure at an equalradial distance from said first axis of rotation.
 6. The device of claim1, wherein each container holder comprises: a generally cylindricalmember having an open top end for receiving and holding a container; anda container retainer spring spanning a lateral slot formed in a sideportion of said cylindrical member for holding the container within saidcylindrical member.
 7. The device of claim 6, wherein said containerholder mounting assembly comprises: a vertical shaft rotatably mountedin said turntable structure; and and a shaft block assembly adapted formounting said cylindrical member to said vertical shaft, said shaftblock assembly comprising: a block structure having curved end portionswhich conform to an inside wall of said cylindrical member, a generallycircular aperture for receiving said vertical shaft, a first slotextending from said aperture to an end of said block structure, and asecond slot extending from an edge of said block structure generallyperpendicularly to said first slot so as to define a cantilevered arm;and a screw extending through a through-hole formed laterally throughsaid block structure, across said first slot, and into an aligned,threaded hole formed laterally through said cantilevered arm so that assaid screw is tightened, said cantilevered arm deflects in such a manneras to tighten said aperture around said vertical shaft.
 8. The device ofclaim 1, wherein said rotational motion coupling elements comprise: aplanetary gear operatively associated with each of said one or morecontainer holders so as to be rotatable therewith; and a sun gear fixedwith respect to said turntable structure, each said planetary gear beingoperatively engaged with said sun gear so that rotation of saidturntable structure about said first axis of rotation causes acorresponding rotation of each said planetary gear and associatedcontainer holder about said second axis of rotation.
 9. The device ofclaim 1, further comprising a bar code scanner mounted adjacent saidturntable structure and constructed and arranged to scan bar codeinformation on a container carried in said container holder.
 10. Thedevice of claim 1, further comprising a sensor system constructed andarranged to determine the rotational position of said turntablestructure.
 11. The device of claim 10, wherein said sensor systemcomprises: four optical sensors fixed with respect to said turntablestructure and mounted adjacent thereto at 90 degree intervals; and asensor tab fixed to said turntable structure and positioned so as toactivate each of said four optical sensors in sequence during rotationof said turntable structure.
 12. The device of claim 11, wherein saidtab is fixed to said turntable structure at a location corresponding toa one of said container holders.
 13. The device of claim 11, whereinsaid turntable structure is in the form of a right angle crosscomprising four 90 degree-spaced arms extending radially from said firstaxis of rotation, and said sensor tab extends from a one of said fourarms.
 14. The device of claim 13, further comprising an extensionconnected to the end of one of said four arms, making said arm to whichsaid extension is attached longer than the other three arms, whereinsaid sensor tab is connected to said extension.
 15. A device foragitating the fluid contents of at least one container, said devicecomprising: a turntable structure constructed and arranged to berotatable about a first axis of rotation; four container holders, eachof said container holders having an axis of rotation and beingconstructed and arranged to hold a container therein, said containerholders being mounted on said turntable structure so as to be rotatabletherewith and so that said axis of rotation of each container holder isgenerally parallel to said first axis of rotation, said containerholders being mounted on said turntable structure at equal radialdistances from said first axis of rotation, each of said containerholders comprising a generally cylindrical member having an open top endfor receiving and holding a container and a container retainer springspanning a lateral slot formed in a side portion of said cylindricalmember for holding the container within said cylindrical member; acontainer holder mounting assembly associated with each containerholder, said container holder mounting assembly being constructed andarranged to mount said associated container holder to said turntablestructure and to permit said associated container holder to rotate abouta second axis of rotation that is generally parallel to and spaced fromboth said first axis of rotation and said axis of rotation of saidassociated container holder; and rotational motion coupling elementsoperatively associated with said turntable structure and said containerholder mounting structure and constructed and arranged to cause eachcontainer holder to rotate about said second axis of rotation as saidturntable structure rotates about said first axis of rotation.
 16. Adevice for agitating the fluid contents of at least one container, saiddevice comprising: a turntable structure constructed and arranged to berotatable about a first axis of rotation; four container holders, eachof said container holders having an axis of rotation and beingconstructed and arranged to hold a container therein, said containerholders being mounted on said turntable structure so as to be rotatabletherewith and so that said axis of rotation of each container holder isgenerally parallel to said first axis of rotation, said containerholders being mounted on said turntable structure at equal radialdistances from said first axis of rotation, each of said containerholders comprising a generally cylindrical member having an open top endfor receiving and holding a container and a container retainer springspanning a lateral slot formed in a side portion of said cylindricalmember for holding the container within said cylindrical member; acontainer holder mounting assembly associated with each containerholder, said container holder mounting assembly being constructed andarranged to mount said associated container holder to said turntablestructure and to permit said associated container holder to rotate abouta second axis of rotation that is generally parallel to and spaced fromboth said first axis of rotation and said axis of rotation of saidassociated container holder; and rotational motion coupling elementsoperatively associated with said turntable structure and said containerholder mounting structure and constructed and arranged to cause eachcontainer holder to rotate about said second axis of rotation as saidturntable structure rotates about said first axis of rotation, whereinsaid rotational motion coupling elements comprise: a planetary gearoperatively associated with each of said four container holders so as tobe rotatable therewith; and a sun gear fixed with respect to saidturntable structure, each said planetary gear being operatively engagedwith said sun gear so that rotation of said turntable structure aboutsaid first axis of rotation causes a corresponding rotation of each saidplanetary gear and associated container holder about said second axis ofrotation.
 17. A device for agitating the fluid contents of at least onecontainer, said device comprising: a turntable structure constructed andarranged to be rotatable about a first axis of rotation; four containerholders, each of said container holders having an axis of rotation andbeing constructed and arranged to hold a container therein, saidcontainer holders being mounted on said turntable structure so as to berotatable therewith and so that said axis of rotation of each containerholder is generally parallel to said first axis of rotation, saidcontainer holders being mounted on said turntable structure at equalradial distances from said first axis of rotation; a container holdermounting assembly associated with each container holder, said containerholder mounting assembly being constructed and arranged to mount saidassociated container holder to said turntable structure and to permitsaid associated container holder to rotate about a second axis ofrotation that is generally parallel to and spaced from both said firstaxis of rotation and said axis of rotation of said associated containerholder; and rotational motion coupling elements operatively associatedwith said turntable structure and said container holder mountingstructure and constructed and arranged to cause each container holder torotate about said second axis of rotation as said turntable structurerotates about said first axis of rotation, wherein said rotationalmotion coupling elements comprise: a planetary gear operativelyassociated with each of said four container holders so as to berotatable therewith; and a sun gear fixed with respect to said turntablestructure, each said planetary gear being operatively engaged with saidsun gear so that rotation of said turntable structure about said firstaxis of rotation causes a corresponding rotation of each said planetarygear and associated container holder about said second axis of rotation.18. A device for agitating the fluid contents of at least one container,said device comprising: a turntable structure constructed and arrangedto be rotatable about a first axis of rotation; one or more containerholders, each of said container holders having an axis of rotation andbeing constructed and arranged to hold a container therein, saidcontainer holders being mounted on said turntable structure so as to berotatable therewith and so that said axis of rotation of each containerholder is generally parallel to said first axis of rotation, each ofsaid container holders comprising a generally cylindrical member havingan open top end for receiving and holding a container and a containerretainer spring spanning a lateral slot formed in a side portion of saidcylindrical member for holding the container within said cylindricalmember; a container holder mounting assembly associated with eachcontainer holder, said container holder mounting assembly beingconstructed and arranged to mount said associated container holder tosaid turntable structure and to permit said associated container holderto rotate about a second axis of rotation that is generally parallel toand spaced from both said first axis of rotation and said axis ofrotation of said associated container holder; and rotational motioncoupling elements operatively associated with said turntable structureand said container holder mounting structure and constructed andarranged to cause each container holder to rotate about said second axisof rotation as said turntable structure rotates about said first axis ofrotation, wherein said rotational motion coupling elements comprise: aplanetary gear operatively associated with each said container holder soas to be rotatable therewith; and a sun gear fixed with respect to saidturntable structure, each said planetary gear being operatively engagedwith said sun gear so that rotation of said turntable structure aboutsaid first axis of rotation causes a corresponding rotation of each saidplanetary gear and associated container holder about said second axis ofrotation.
 19. A method for agitating the fluid contents of a containerhaving an axis of rotation comprising: rotating the container about afirst axis of rotation that is parallel to the axis of rotation of thecontainer and spaced apart from the axis of rotation of the container;and simultaneously rotating the container about a second axis ofrotation that is parallel to the axis of rotation of the container andis offset from the axis of rotation of the container and the first axisof rotation.
 20. The method of claim 19, wherein the fluid contents ofsaid container include a solid support material for binding andimmobilizing a target analyte which may be present in a sample.
 21. Themethod of claim 20, wherein said solid support material includesmagnetically responsive particles.
 22. The method of claim 21, whereinsaid target analyte is a target nucleic acid.
 23. The method of claim22, wherein the fluid contents of said container further include apolynucleotide capture probe which hybridizes to a target nucleotidebase sequence region present in said target nucleic acid under a firstset of predetermined hybridization conditions.
 24. The method of claim23, wherein said magnetically responsive particles include animmobilized polynucleotide which hybridizes to said polynucleotidecapture probe under a second set of predetermined hybridizationconditions.
 25. The method of claim 24 further comprising: withdrawingan aliquot of the fluid contents of said container; providing saidaliquot to said sample, said sample being present in a reactionreceptacle; and exposing said sample to said first and second sets ofpredetermined hybridization conditions.
 26. The method of claim 25further comprising subjecting said sample to a magnetic field, therebyisolating said magnetically responsive particles within said reactionreceptacle.
 27. The method of claim 26 further comprising separating atleast a portion of said sample from said magnetically responsiveparticles isolated within said reaction receptacle, thereby separatingnon-target nucleic acid from target nucleic acid which may be present insaid sample.
 28. The method of claim 27 further comprising determiningthe presence or absence of said target nucleic acid in said sample as anindication of the present or absence of an organism or virus or one ormore members of a group of organisms or viruses in said sample.
 29. Themethod of claim 28 further comprising amplifying said target nucleotidebase sequence region prior to said determining step.
 30. The method ofclaim 19, wherein the fluid contents of said container includetarget-capture means.